0000000000478870
AUTHOR
Letizia Scola
THE METABOLIC SYNDROME: IL-10 POLYMORPHISMS INFLUENCE ON SEROLOGICAL AND HAEMATOLOGICAL PARAMETERS IN TYPE 2 DIABETES.
Regulatory cytokine gene polymorphisms and risk of colorectal carcinoma.
It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori-associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease-associated colorectal cancer. Growing evidence suggests that these associations might be not casual findings. Focusing on individual cytokines has generated evidence that anti-inflammatory cytokine interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) may have a complex role in gastrointestinal carcinogenesis. As an example, IL-10-deficient mice develop severe atrophic gastritis and a chronic enterocolitis, develo…
Search for genetic factors associated with susceptibility to multiple sclerosis.
Multiple sclerosis (MS) is a cell-mediated autoimmune disease characterized by type-1 cytokine production. Environmental and individual genetic background might influence this response particularly in cytokine gene polymorphisms. We evaluated whether polymorphisms of interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-alpha genes, which might play a role in MS pathogenesis, are associated with MS susceptibility. Genotype frequencies for all the analyzed polymorphisms were not differently distributed between cases and controls. It is reasonable to suppose that the cytokine single-nucleotide polymorphisms (SNPs) studied must be considered against a larger genetic background involving …
Valutazione della “gene expression” di Citochine e loro recettori in soggetti dediti ad attività sportiva.
Analysis of HLA-DQA, HLA-DQB frequencies in a group of Sardinian centenarians
Human leukocyte antigen (HLA) alleles, regulating type and intensity of the immune response, might influence life expectancy. In previous case-control studies the authors have demonstrated that both HLA-DR and -DQ alleles are not associated with longevity in the Sardinian population. On the other hand, association studies are subjected (as part of the homogeneity of the population in terms of geographic origin) to a number of possible confounding factors. Therefore, the authors typed the HLA-DQA1 and HLA-DQB1 alleles in 24 sibs (age range 85 to 97) of 17 centenarians by PCR-SSP. Sib pair analysis showed non-significant differences between the observed and expected percentage of DQA* or DQB1…
Studio delle frequenze alleliche di +1188 A/C di IL12B (p40) in soggetti affetti da Sclerosi Multipla.
Genetic Background of Centenarians May Be Protective Against Cardiovascular Diseases.
IL-10 and TNF-α polymorphisms in a sample of sicilian patients affected by tuberculosis: implication for ageing and life span expectancy
Abstract Human longevity seems to be directly correlated with optimal functioning of the immune system, suggesting that some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses, in particular cytokine gene polymorphisms. In fact, modification of cytokine network is a constant report in studies on age related modification of immune response. Moreover cytokine polymorphisms studies are indicating their involvement in the reshaping of cytokines network as an integral part of the scenario related to a successful ageing. A particular role might be attributed to the influence of cytokine polymorphisms on the efficiency o…
Genetic and Epigenetic Factors of Takotsubo Syndrome: A Systematic Review
Takotsubo syndrome (TTS), recognized as stress’s cardiomyopathy, or as left ventricular apical balloon syndrome in recent years, is a rare pathology, described for the first time by Japanese researchers in 1990. TTS is characterized by an interindividual heterogeneity in onset and progression, and by strong predominance in postmenopausal women. The clear causes of these TTS features are uncertain, given the limited understanding of this intriguing syndrome until now. However, the increasing frequency of TTS cases in recent years, and particularly correlated to the SARS-CoV-2 pandemic, leads us to the imperative necessity both of a complete knowledge of TTS pathophysiology for identifying bi…
The Genetics of Innate Immunity and Inflammation in Ageing, Age-Related Diseases and Longevity
Inflammation is a key component of age-related diseases such as atherosclerosis and Alzheimer’s disease (AD) and genes coding for inflammatory or anti-inflammatory molecules are, therefore, good candidates for influencing the risk of developing these pathologies. Findings discussed in this chapter suggest that different alleles of genes coding for pro-or anti-inflammatory genes may affect individual life-span expectancy by influencing the type and intensity of immune-inflammatory responses against environmental stressors involved in the development of age-related disease. Our immune system has evolved to control pathogens and so pro-inflammatory responses are likely to be evolutionarily pro…
Allele frequencies of +874T→A single nucleotide polymorphism at the first intron of interferon-γ gene in a group of Italian centenarians
Ageing is characterized by a pro-inflammatory status which could contribute to the onset of major age-related diseases such as cardiovascular diseases, neurodegeneration, osteoarthritis and osteoporosis, and diabetes. Thus, it can be hypothesized that genetic variations in pro- or anti-inflammatory cytokines might influence successful ageing and longevity. We have studied the distribution of +874T--A interferon-gamma (IFN-gamma) polymorphisms in a large number of Italian centenarians to evaluate if the two alleles might be differently represented in people selected for longevity. DNA samples were obtained from 174 Italian centenarians (99 years old, 142 women and 32 men) and from 24860-year…
Genetic Determined Downregulation of Both Type 1 and Type 2 Cytokine Pathways Might Be Protective against Pancreatic Cancer
Many cytokine polymorphisms have been studied for associations with susceptibility to breast, gastric, liver, lung, prostate, and ovarian cancer without conclusive results. The cytokine network, indeed, is characterized by complex interactions, and the final biological effect of a single genetic variation depends on the balance among different molecular signals. As is well known, Th1/Th2 cytokine unbalanced production might predispose to different pathologies, cancer included. In general, a prolonged type 1 inflammatory response might allow that cells accumulating enough "genetic hits" are promoted to neoplastic transformation. On the other hand, IL-13-producing cells through the IL-13/IL-4…
Gender-specific association between -1082 IL-10 promoter polymorphism and longevity.
Ageing is characterized by a pro-inflammatory status, which could contribute to the onset of major age-related diseases. Thus, genetic variations in pro- or anti-inflammatory cytokines might influence successful ageing and longevity. IL-10 is an appropriate candidate because it exerts powerful inhibitory effects on pro-inflammatory function. IL-10 production is controlled by several polymorphic elements in the 5' flanking region of IL-10 gene on 1q32 locus, involving alleles at two microsatellite regions and several polymorphisms in promoter region. We analysed in 190 Italian centenarians (99 years old, 159 women and 31 men) and in 26060 years old control subjects (99 women and 161 men), ma…
Interleukin-10 promoter polymorphism in sporadic Alzheimer's disease.
Proinflammatory cytokines and acute-phase proteins play an important role in Alzheimer's disease (AD) neurodegeneration, and common polymorphisms of genes controlling their high production have been shown to be associated with AD. Thus, AD patients display a proinflammatory genotype and the control of inflammation might play a protective role in AD development. By sequence-specific probes, we have evaluated the role of anti-inflammatory cytokine interleukin(IL)-10 in AD, by analysing in 132 AD patients and 213 healthy controls the prevalence of three different haplotypes, involving three single-nucleotide polymorphisms (SNPs) at -1082 (G--A), -819 (C--T) and -592 (C--A) nucleotides of IL-10…
Cytokine serum profile in a group of Sicilian Nonagenarians
The aim of our study was to evaluate the possibility of using multiplex analysis of the cytokine profile as a marker for successful aging by comparing cytokine plasmatic levels of a group of Sicilian nonagenarians with those of young controls. We analyzed a panel of 17 cytokines, comprehensive of haematopoietic factors T helper 1 (Th1), Th2, inflammation regulatory cytokines, and chemokines. The assay was carried out using the Luminex system. Interleukin (IL)-6 levels (p = 0.01) were increased in nonagenarians, whereas no modifications of other proinflammatory cytokines and chemokines were observed. Interferon-gamma (IFN-gamma) and IL-2 levels are unmodified, suggesting a substantial mainte…
Training Effects on Laboratory Parameters Are Independent of Genetic Polymorphisms of IL-10 and TNF-alpha (TNF-α)
Background: It is well known that exercise has beneficial effects on health. Although intense exercise is experienced by the body as a condition of stress, a well designed training has long term beneficial effects on the organism of an athlete. Less is known about the effects that the genetic background might have on training adaptation and on the consequent modification of laboratory parameters. Methods: In our study we evaluated the blood chemistry parameters of a group of 41 athletes compared with a group of 45 amateur athletes, to assess whether the training has effects on their variation. In addition we typed our subjects for polymorphisms 308 A/G of the tumor necrosis factor-α (TNF-α)…
Analisi dei Polimorfismi di Citochine Th2 nella Sclerosi Multipla.
Valutazione delle frequenze alleliche e genotipiche di citochine di tipo Th1 e Th2 in pazienti affetti da malattia di Behçet.
Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10 -1082 promoter SNP and its interaction with TNF-alpha -308 promoter SNP.
Ageing is associated with chronic, low grade inflammatory activity leading to long term tissue damage, and systemic chronic inflammation has been found to be related to mortality risk from all causes in older persons.1 Also, the genetic constitution of the organism interacting with systemic inflammation may cause defined organ specific illnesses. Thus, age related diseases such as Alzheimer’s disease (AD), Parkinson’s disease, atherosclerosis, type 2 diabetes, sarcopenia, and osteoporosis, are initiated or worsened by systemic inflammation, suggesting the critical importance of unregulated systemic inflammation in the shortening of survival in humans.1–3 Accordingly, proinflammatory cytokin…
Analysis of HLA-DRB1,DQA1,DQB1 haplotypes in Sardinian centenarians
Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1 *15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a ro…
Tumor necrosis-factor-alpha -308 A/G polymorphism is associated with age at onset of Alzheimer's disease.
Abstract Pro-inflammatory cytokines and acute-phase proteins play an important role in Alzheimer's disease (AD) neurodegeneration, and common polymorphisms of genes controlling their production have been shown to be associated with AD. Tumor necrosis factor (TNF)-α is an inflammatory cytokine involved in the local immune response occurring in the central nervous system of AD patients. Genetic variation could contribute to the risk of developing AD or influence the age at the onset of the disease. We genotyped 222 patients (152 women, 70 men; age range 60–87) and 240 non-demented age-matched healthy controls for TNF-α −308 G/A single nucleotide polymorphism (SNP). No significant differences …
The Ferroxidase Hephaestin in Lung Cancer: Pathological Significance and Prognostic Value
AbstractIron is a fundamental nutrient utilized by living cells to support several key cellular processes. Despite its paramount role to sustain cell survival, excess of labile iron availability can inflict severe cell damage via reactive oxygen species generation which, in turn, can promote neoplastic transformation. The lung is particularly sensitive to iron-induced oxidative stress, given the high oxygen tensions herein present. Moreover, cigarette smoke as well as air pollution particulate can function as vehicles of iron supply, leading to an iron dysregulation condition shown to be crucial in the pathogenesis of several respiratory diseases including lung cancer. Hephaestin (HEPH) bel…
Polymorphisms of genes of TGF-beta pathway and susceptibility to colorectal cancer
Background: Genetic background implicated in cytokine network may have a key role in the susceptibility to colorectal cancer (CRC). The TGF-β pathway is involved in several biological processes, including cell proliferation, differentiation, migration and apoptosis. Methods: rs1800471 SNP polymorphism of TGF-ß1 rs334348 and rs334349 of TGF-βR1, rs900 of TGF-β2 and rs4522809 of TGF-β2R2 were typed in a group of 82 patients affected by sporadic CRC and in 237 age- and sex-matched healthy controls, using a competitive allele specific PCR assays (KASPar), developed by KBioscience (England). Results: No significant genetic contribution has been observed for 3 of the 5 SNPs tested. Indeed, a sign…
POTENTIAL NEW GENETIC AND BIOCHEMICAL MARKERS OF CHRONIC KIDNEY FAILURE
disease (CKD) is an important source of long-term morbidity and mortality. It has been estimated that CKD affects more than 20 million people in the United States. Given that most patients are asymptomatic until the disease has significantly progressed, they remain unaware of the condition. Thus, it is essential to have clinical practice guidelines (BIOMARKERS aimed at early detection, evaluation, diagnosis, and treatment of this condition.
In vitro treatment with interleukin-2 normalizes type-1 cytokine production by lymphocytes from elderly
The term immunosenescence is taken to mean the deterioration of immune function seen in elderly, which is manifested in increased susceptibility to infectious diseases, neoplasias, and autoimmune diseases. It is only recently that we have begun to understand the cellular and molecular changes involved. Of special interest in this regard are observations of a decline in synthesis of Type-1 cytokines which predisposes to diminished cell mediated immunity. We have evaluated the production of type 1 cytokines in old and young donors either in presence or in absence of recombinant interleukin-2 (rIL-2). Lymphocytes were stimulated with plastic bound anti-CD3 and after 48 h the supernatants were …
Association between longevity and cytokine gene polymorphisms. A study in Sardinian centenarians
Background and aims: Human longevity seems to be directly correlated with optimal functioning of the immune system, suggesting that some genetic determinants of longevity reside in those polymorphisms for the immune system genes which regulate immuneinflammatory responses, in particular cytokine gene polymorphisms. The frequency of − 174C single nucleotide polymorphism (SNP) in the promoter region of the interleukin(IL)-6 gene is increased in Italian male centenarians. Moreover, the frequency of − 1082G SNP at the 5′ flanking region of the IL-10 gene coding sequence is increased among male centenarians, and that of +874A SNP at the interferon (IFN)- γ gene was found more frequently in femal…
Looking for immunological risk genotypes
Pro-inflammatory genetic background and zinc status in old atherosclerotic subjects.
Inflammation and genetics are prominent mechanisms in the pathogenesis of atherosclerosis (AT) and its complications. In this review we discuss the possible impact on AT development of several genetic determinants involved in inflammation, oxidative stress and cytoprotection (IL-6, TNF-alpha, IL-10, CD14, TLR4, MT, HSP70). Genetic polymorphisms of these genes may affect a differential inflammatory response predisposing to AT. However, allelic polymorphisms of genes which increase the risk of AT frequently occur in the general population but, only adequate gene-environment-polymorphism interactions promote the onset of the disease. Zinc deficiency has been suggested as an environmental risk …
Role of prothrombotic polymorphisms in successful or unsuccessful aging.
The study of the genetic profile of centenarians aims to identify the genes and allelic variants which may influence a greater life expectancy and that can be considered as predisposing factors associated to the aging diseases, such as Alzheimer. Centenarians, that represent a cohort of selected survivors, show an hypercoagulability state characterised by striking signs of high coagulation enzyme activity, as directly assessed by the tested higher plasma level of some important factors involved in the haemostasis balance. Anyway, these individuals seem to have a reduced susceptibility to dementia, as well as to cardiovascular events. In this study we analyze the frequencies of Leiden Factor…
Looking for Immunological Risk Genotypes
Several functional markers of the immune system may be used either as markers of successful aging or conversely as markers of unsuccessful aging. Particularly, a combination of high CD8 and low CD4 and poor T cell proliferation has been associated with a higher two-year mortality in very old subjects. Therefore, genetic determinants of longevity should reside in those polymorphisms for the immune system genes that regulate immune responses. Concerning these changes in T cell subpopulations, how much they depend on the immunogenetic background and how much they depend on individual antigenic load, such as chronic infections, should be assessed. As previously demonstrated in our population, t…
Analisi del Profilo genetico Th1/Th2 in soggetti allergici.
Immunological and immunogenetic markers in sporadic Alzheimer’s disease
Background: Common polymorphisms of genes controlling inflammation-modulating cytokines and acute-phase proteins which play important roles in the pathogenesis of Alzheimer''s disease (AD) have been shown to be associated with AD. Aims: The immunological and immunogenetic markers potentially useful for the AD risk evaluation and diagnosis are briefly reviewed. Conclusion: The state-of-the-art of immunological and immunogenetic markers of AD indicates that new tools and strategies are necessary to identify gene products useful as diagnostic tools.
Apolipoprotein E Genotypic Frequencies Among Down Syndrome Patients Imply Early Unsuccessful Aging for ApoE4 Carriers
Down syndrome (DS) might be considered a model for unsuccessful and early aging, possibly accelerated for those who carry the APOE4 allele associated with common age-related diseases, e.g., Alzheimer's disease and a poor prognosis after acute myocardial infarction, causing lower ApoE4 frequencies among the very old in general populations. We compared ApoE genotypic frequencies found for healthy adults (n = 211, age 90) to those found for DS patients (n = 106, mean age 9 years), all living in western Sicily. We found that the frequency of the ApoE23 genotype increased with age among the healthy adults (8.5%, 6.4%, 19.7%; p = 0.024) while ApoE34 frequency decreased (16.1%, 12.6%, 4.1%; p = 0.…
Study of the Association with -330T/G IL-2 in a Population of Centenarians from Centre and South Italy.
Immune response in elderly is characterised by a progressive loss of the ability to cope environmental stressors with a characteristic remodelling of cytokine network. One of the data constantly reported in literature is the decrease of IL-2 production. An IL-2 central role in the reconstitution of T cell function in vitro is largely documented. Studies on a T → G polymorphism at - 330 nt of IL-2 gene promoter region have demonstrated that T lymphocytes from 330GG homozygous subjects are able to produce in vitro higher amount of IL-2, than -330TG heterozygous or -330TT homozygous subjects. As a genetic background conditioning the maintaining of an efficient immune response would exert posit…
Myocardial infarction marker levels are influenced by prothrombin and tumor necrosis factor-α gene polymorphisms in young patients.
Polymorphisms of genes encoding key factors for the control and activation of inflammatory response and coagulation cascade regulation may play a role in genetic susceptibility to acute myocardial infarction (AMI). This study sought to analyze the effect of TNF - 308G/A and pro-thrombin (FII) 20210G/A polymorphisms on the laboratory parameters of young patients affected by AMI. Results indicated that TNF - 308A positive genotype frequencies were increased in these patients and that a genetically determined higher production of TNF-alpha is associated in young subjects to a more severe cardiac damage as depicted by higher levels of troponin, Creatine kinase-MB Isoenzyme (mCK-MB) and a signif…
Frequency of polymorphisms of signal peptide of TGF-beta1 and -1082G/A SNP at the promoter region of Il-10 gene in patients with carotid stenosis
The role of inflammation in atherosclerosis is well recognized. We have evaluated the allele frequencies of the +869T/C and +915G/C polymorphisms (SNPs) at the TGF-beta1 gene and -1082G/A SNP at IL-10 promoter sequence, two well-known immunosuppressive and anti-inflammatory cytokines, in patients with carotid stenosis. Our data suggest a lack of association between these SNPs and the susceptibility to atherosclerosis although other reports have demonstrated this association. These results may be due to the pleiotropic effects of the cytokines and/or differences in haplotype combination that should be investigated to elucidate the role of TGF-beta1 and IL-10 polymorphisms in atherosclerosis.
Pathological implications of Th1/Th2 cytokine genetic variants in Behçet's disease: Data from a pilot study in a Sicilian population
Cytokines act as pleiotropic polypeptides able to regulate inflammatory/immune responses and to provide important signals in physiological and pathological processes. Several cytokines (Th1, Th2, and Th17) seem to be involved in the pathophysiology of Behçet's disease, a chronic immune-mediated disease characterized by oral and genital lesions and ocular inflammation. Its individual susceptibility seems to be modulated by genetic variants in genes codifying these cytokines. Th1 and Th17 seem to be involved in the disease's active phases, and Th2 seems to affect the development or severity of the disease; however, contrasting data are reported. In this study, some genetic variants of the Th1…
Evaluation of cytokine polymorphisms (TNFalpha, IFNgamma and IL-10) in Down patients with coeliac disease.
Abstract Background In Down syndrome there is an increased prevalence of coeliac disease, but the reasons for this association are yet unknown. Aims To evaluate a possible correlation between TNFα, IFNγ and IL-10 genotype polymorphisms with the susceptibility to coeliac disease in Down syndrome patients. Methods Single nucleotide polymorphisms of TNFα (−308G → A promoter region), IFNγ (+874T → A promoter region) and IL-10 (−1082G → A promoter region) have been studied in 10 Down patients with coeliac disease, in 40 Down patients without coeliac disease and in 220 healthy controls. Clinical features were also studied in coeliac disease–Down syndrome patients. Results The 10 coeliac disease–D…
Analysis of the Polymorphisms of Th1 and Th17 Cytokines in Mediterranean Spotted Fever
Background: We have recently reported that the susceptibility for Mediterranean spotted fever (MSF) caused by Rickettsia conorii, is influenced by the Th2 and Th1 cytokine genetic polymorphism profiles. Less it is known on the effect of gene polymorphisms of cytokine produced by the Th17. Methods: 70 Sicilian patients affected by MSF and 239 control subjects matched for age, gender, and geographic origin were typed for functionally relevant single nucleotide polymorphisms (SNPs) of IFN-γ (+874 T/A), IL-18 (-137 G/C and -607A/C ) and IL-17 (7488T/C) according to our laboratory procedures. Results: No significant differences in IL-18 -137 G/C, -607A/C and in IFN-γ +874 T /A genotype frequenci…
POLYMORPHISMS IN TYPE 1 AND TYPE 2 CYTOKINE GENES MIGHT PLAY COMPLEMENTARY ROLE IN PANCREATIC CANCER SUSCEPTIBILITY.
Immunosenescence and anti-immunosenescence therapies: the case of probiotics.
ABSTRACT Aging is a complex process that negatively impacts the development of the immune system and its ability to function. Progressive changes in the T and B cell systems over the life span have a major impact on the capacity to respond to immune challenge. These cumulative age-associated changes in immune competence are termed immunosenescence. This process is mostly characterized by: (1) shrinkage of the T cell repertoire and accumulation of oligoclonal expansions of memory/effector cells directed toward ubiquitary infectious agents; (2) involution of the thymus and the exhaustion of naive T cells; and (3) chronic inflammatory status. Here we discuss possible strategies to counteract t…
Autoantibody production in aging: effect of cytokine gene polymorphisms in Sicilian ultra-nonagenarians
Cytokine Polymorphism in Takotsubo Cardiomyopathy
IMIN11. Cytokine Polymorphism in Takotsubo Cardiomyopathy P. Di Gangi1, L. Scola1, S. Giambanco1, M. Bova1, G. Santini1, L. Vaccarino1, C. R. Balistreri1, D. Lio1, P. Assennato1, S. Novo1, G. Novo1 1University of Palermo, Palermo, Italy Background: Takotsubo (TT) cardiomyopathy is characterised by an acute left ventricular dysfunction triggered by emotional or physical stresses. Clinically, the syndrome is characterised by acute symptoms mimicking acute infarction without relevant electrocardiographic and biochemical markers of myocardial damage changes. Stressful events inducing an excess catecholamine release and myocardial β-adrenergic receptors (β-AR) seem to play a major role in TT. Ac…
Associazione dei polimorfismi dei geni INF-γ ed IL-10 con la suscettibilità alla Febbre bottonosa.
TGF-B pathway polymorphisms as markers for gender differential susceptibility to sporadic thoracic aortic aneurysm
Relevance of gamma interferon, tumor necrosis factor alpha, and interleukin-10 gene polymorphisms to susceptibility to Mediterranean spotted fever.
Several studies have demonstrated that cellular immunity plays a critical role in the protective immune response against Rickettsia conorii. Immune CD4+ and CD8+ T cells are both involved in the control of rickettsial infection (38). Perivascular infiltrated CD4+ and CD8+ T lymphocytes, macrophages, and natural killer cells produce chemokines and cytokines that activate endothelial rickettsicidal activities. Infected human cells, including endothelial cells, hepatocytes, and macrophages, activated by gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β), kill intracellular rickettsiae by one or a combination of three mechanisms, involving nitric oxide syn…
Role of TLR Polymorphisms in Immunosenescence
Innate immunity provides a first line of host defense against infection through microbial recognition and killing while simultaneously activating a clonotypic immune response. Toll-like receptors (TLRs) are principal mediators of rapid microbial recognition and function mainly by detection of pathogen-associated molecular patterns (PAMPs) that do not exist in the host. The different members of TLRs recognize several PAMPs, such as peptidoglycan for TLR2, lipopolysaccharide (LPS) for TLR4, flagellin for TLR5, and CpGDNA-repeats for TLR9. Several endogenous ligands of various TLRs have been also identified in the host. In this chapter, we describe the involvement of TLR-4 polymorphisms in imm…
On the Road to Accurate Biomarkers for Cardiometabolic Diseases by Integrating Precision and Gender Medicine Approaches
The need to facilitate the complex management of cardiometabolic diseases (CMD) has led to the detection of many biomarkers, however, there are no clear explanations of their role in the prevention, diagnosis or prognosis of these diseases. Molecules associated with disease pathways represent valid disease surrogates and well-fitted CMD biomarkers. To address this challenge, data from multi-omics types (genomics, epigenomics, transcriptomics, proteomics, metabolomics, microbiomics, and nutrigenomics), from human and animal models, have become available. However, individual omics types only provide data on a small part of molecules involved in the complex CMD mechanisms, whereas, here, we pr…
Cytokine genotyping (TNF and IL-10) in patients with celiac disease and selective IgA deficiency
Selective IgA deficiency (IgAD) and celiac disease (CD) are frequently associated and share the ancestral haplotype human leukocyte antigen (HLA)-8.1, which is characterized by a peculiar cytokine profile. The aim of this study was to evaluate the role of tumor necrosis factor (TNF) and interleukin (IL)-10 alleles in CD and CD-IgAD.The distribution of some biallelic polymorphisms of both cytokine promoters (-308G--A and -863C--A at TNF promoter sequence and -1082G--A, -819C--A, and -592C--T at IL-10 promoter) were typed using biotilinated specific probes in 32 celiac patients, in 34 CD-IgAD patients, and in 96 healthy controls.In CD and CD-IgAD, the -308A allele was significantly more frequ…
IL-10 and TNF-α polymorphisms and the recovery from HCV infection
Hepatitis C virus (HCV) infection becomes chronic in about 85% of infected individuals, whereas only 15% of infected people clear spontaneously the virus. It is conceivable that the host immunogenetic background influences the course of infection in term of recovery. Thus, in this study we have evaluated the effect of functionally relevant polymorphisms at tumor necrosis factor-alpha (TNF-alpha, i.e., 2 biallelic polymorphisms at nt -863 and nt-308 of the promoter) and interleukin-10 (IL-10) loci (i.e., 1 biallelic polymorphism at nt -1082 of the promoter), on the clearance of HCV infection. To this purpose, we compared 18 Sicilian patients who had spontaneously recovered from previous HCV …
Single nucleotide polymorphisms (SNPs) of pro-inflammatory/anti-inflammatory and thrombotic/fibrinolytic genes in patients with acute ischemic stroke in relation to TOAST subtype.
Abstract Background The genetic basis of complex diseases like ischemic stroke probably consists of several predisposing risk factors, such as genes involved in inflammation and thrombotic pathways. On this basis the aim of our study was to evaluate the role of SNPs (single nucleotide polymorphisms) of some pro-inflammatory/anti-inflammatory and coagulation/fibrinolytic genes in patients with acute ischemic stroke. Methods The study population consisted of 144 consecutive Caucasian adult patients who were hospitalized in the Internal Medicine Department at the University of Palermo between November 2006 and January 2008, and who met inclusion criteria. The cases were patients admitted with …
Analysis of Polymorphism C558T of MAL (TIRAP) in Mediterranean Spotted Fever
Analysis of Polymorphism C558T of MAL (TIRAP) in Mediterranean Spotted Fever M. Bova1, L. Scola1, C. Colomba1, L. Vaccarino1, P. Di Gangi1, G. Santini1, G. Giammanco1, C. R. Balistreri1, D. Lio1, L. Titone Lanza Di Scalea1 1University of Palermo, Palermo, Italy Background: In our previous studies, we have demonstrated that cytokine polymorphisms, such as IFNγ +874T/A or IL-17 SNP (7488T/C), might interfere with R. Conorii infection control. In addition, we have reported that +896A/G TLR4 SNP is a component of a genetic background that might influence the clinical outcome of Boutonneuse fever (Mediterranean spotted fever, MSF). The +869G allele, that attenuates receptor signaling, was actual…
MIF rs755622 and IL6 rs1800795 Are Implied in Genetic Susceptibility to End-Stage Renal Disease (ESRD)
Chronic kidney disease (CKD) is characterized by an increased risk of kidney failure and end-stage renal disease (ESRD). Aging and comorbidities as cardiovascular diseases, metabolic disorders, infectious diseases, or tumors, might increase the risk of dialysis. In addition, genetic susceptibility factors might modulate kidney damage evolution. We have analyzed, in a group of ESRD patients and matched controls, a set of SNPs of genes (Klotho rs577912, rs564481, rs9536314; FGF23 rs7955866; IGF1 rs35767; TNFA rs1800629; IL6 rs1800795; MIF rs755622, rs1007888) chosen in relation to their possible involvement with renal disease and concomitant pathologies. Analysis of the raw data did indicate …
Polymorphisms of Pro-Inflammatory IL-6 and IL-1β Cytokines in Ascending Aortic Aneurysms as Genetic Modifiers and Predictive and Prognostic Biomarkers
Background: Previous studies have demonstrated that polymorphisms involved in immune genes can affect the risk, pathogenesis, and outcome of thoracic ascending aortic aneurysms (TAAA). Here, we explored the potential associations of five functional promoter polymorphisms in interleukin-6 (IL-6), IL-1B, IL-1A, IL-18, and Tumor necrosis factor (TNF)A genes with TAAA. Methods: 144 TAAA patients and 150 age/gender matched controls were typed using KASPar assays. Effects on telomere length and levels of TAAA related histopathological and serological markers were analyzed. Results: Significant associations with TAAA risk were obtained for IL-6 rs1800795G>
Role of Cytokine Polymorphisms in the Rhinitis-Asthma Evolution
AAD1. Role of Cytokine Polymorphisms in the Rhinitis-Asthma Evolution G. Santini1, L. Scola1, S. La Piana1, P. Di Gangi1, L. Vaccarino1, M. Bova1, C. R. Balistreri1, D. Lio1, G. Di Lorenzo1 1University of Palermo, Palermo, Italy Background: Several epidemiological studies demonstrate that a timeline from rhinitis to asthma exists, and that rhinitis is a risk factor for asthma. In particular, rhinitis increases the chance of development of asthma by about three times. In addition to environmental factors, genetic factors play an important role in the development of atopic airway diseases. The aim of this study is to analyse the role of cytokine polymorphism in the evolution of rhinitis-asthm…
TNFalfa,IFN gamma, IL-10 gene polymorphisms in a sample of Sicilian patients with coeliac disease
Role of environmental and genetic factor interaction in age-related disease development: the gastric cancer paradigm.
The association of Helicobacter pylori (Hp) infection with gastric cancer is well known and might be considered a paradigmatic example of the role that interaction among environmental factors and individual background might play in inducing age-associated disease. To evaluate the role of interaction of Hp infection with genetic background, gastric cancer and chronic gastritis patients as well as random selected controls were typed for five inflammation-related polymorphisms of IL-1 and IL-10 cytokine genes. No association among IL-10 or IL-1 variants with an increased risk of gastric cancer was found, whereas an Hp-independent association of IL-1beta -511T positive genotypes to an increased…
Laboratory parameters in centenarians of Italian ancestry
Studies aimed at collecting reference parameters for haematochemical analysis in the elderly are scarce and for the oldest old subjects even more rare. In order to establish the reference values for the most common laboratory text in long living individuals, we measured haematochemical parameters in >100 years old subjects and in aged subjects as control. Six hundred and two centenarians accepted to be enrolled in the study. A case history containing the complete anamnesis, clinical examinations, evaluation of the clinical cognitive and functional tests, was prepared for each centenarian. Blood samples from 120 > 100 years old subjects free of chronic or acute Illness (i.e. Alzheimer’s dise…
Polymorphisms of pro-inflammatory genes and prostate cancer risk: a pharmacogenomic approach.
In this paper, we consider the role of the genetics of inflammation in the pathophysiology of prostate cancer (PCa). This paper is not an extensive review of the literature, rather it is an expert opinion based on data from authors' laboratories on age-related diseases and inflammation. The aim is the detection of a risk profile that potentially allows both the early identification of individuals at risk for disease and the possible discovery of potential targets for medication. In fact, a major goal of clinical research is to improve early detection of age-related diseases, cancer included, by developing tools to move diagnosis backward in disease temporal course, i.e., before the clinical…
Susceptibility to Heart Defects in Down Syndrome Is Associated with Single Nucleotide Polymorphisms in HAS 21 Interferon Receptor Cluster and VEGFA Genes
Background: Congenital heart defects (CHDs) are present in about 40&ndash
Frequenze degli aplotipi-1082GA/819CT/592CA della regione promoter del locus IL-10 in campioni di DNA ottenuti da pazienti affetti da Diabete mellito di tipo II.
Studio delle frequenze alleliche del polimorfismo +1902A/G del gene IL4R in soggetti affetti da sclerosi multipla .
Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency
Celiac disease (CD) and selective IgA deficiency (IgAD) are frequently associated, and share the same genetic background. The aim of the present study was to evaluate both Type 1 and 2 plasma cytokine levels in CD and in CD-IgAD. IL-2, TNF-alpha, IL-10, IL-4 and IL-13 plasma levels were measured both at diagnosis and after a gluten-free diet (GFD) in 32 CD patients, in 27 CD-IgAD patients and in 30 healthy controls. IFN-gamma levels were significantly higher in CD and CD-IgAD than in controls, TNF-alpha displayed significantly higher levels in CD-IgAD when compared both with controls and with CD, and IL-2 was in CD-IgAD significantly increased respect to controls. Kinetics of the Type 1 cyt…
Role of environmental and genetic factor interaction in the aging related disease development: The gastric cancer paradigm.
Genotype frequencies of the +874T→A single nucleotide polymorphism in the first intron of the interferon-γ gene in a sample of Sicilian patients affected by tuberculosis
In the light of the key role played by interferon (IFN)-gamma in the control of tuberculosis, in the present paper we have evaluated the distribution of the functional +874T --> A IFN-gamma single nucleotide polymorphism (SNP) in Sicilian patients affected by tuberculosis. Our aim was to determine whether there is an association between the TT genotype, which has been suggested to be linked to an increased production of IFN-gamma, and resistance to chronic tuberculosis. DNA samples were obtained from 45 patients and 97 healthy controls. Polymorphism at +874 was identified using amplification refractory mutational system methodology. The +874T SNP was less frequent in patients than in contro…
Age and Cytokine Gene Variants Modulate the Immunogenicity and Protective Effect of SARS-CoV-2 mRNA-Based Vaccination
The introduction of anti-SARS-CoV-2 vaccines in late 2020 substantially changed the pandemic picture, inducing effective protection in the population. However, individual variability was observed with different levels of cellular response and neutralizing antibodies. We report data on the impact of age, gender, and 16 single nucleotide polymorphisms (SNPs) of cytokine genes on the anti-SARS-CoV-2 IgG titers measured 31 and 105 days after administration of the second dose of BNT162b2 vaccine to 122 healthy subjects from the health care staff of the Palermo University Hospital, Italy. The higher titers at 31 days were measured in the younger subjects and in subjects bearing T-positive genotyp…
Immunogenetic Markers and Sporadic Alzheimer's Disease Diagnostic Knot.
SARS CoV2 infection _The longevity study perspectives
Graphical abstract
Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction.
Thrombotic risk increases in elderly, therefore, the understanding of the genetic predisposition of hypercoagulability could make the difference in the prevention of venous and/or arterial thrombotic events. Laboratory evaluation of hyperfibrinogenemia, increased Factor VII levels, antiphospholipid antibodies presence and hyperhomocysteinemia are considered to have a consistent high predictivity for arterial thrombophilic diseases. Anyway, a large debate exists on the validity of testing Leiden Factor V (FV) G1691A and/or prothrombin (FII) G20210A polymorphisms in patients affected by arterial thrombotic diseases, despite of the several observations described. Here we report data strongly s…
TNFalpha, IFNgamma and IL-10 gene polymorphisms in a sample of Sicilian patients with coeliac disease.
Coeliac disease is associated with DQ2 and DQ8 alleles, but other genes also confer an additional genetic risk.Defining whether the genetic profiles of interleukin-10, tumour necrosis factor alpha and interferon gamma are associated with an increased coeliac disease risk.The functionally gene polymorphisms of tumour necrosis factor alpha (-308G/A), interferon gamma (+874T/A) and interleukin-10 (-1082G/A) were typed using sequence specific primer-polymerase chain reaction in 110 Sicilian coeliac disease patients and in 220 Sicilian healthy controls.No differences in genotype frequencies of interleukin-10 polymorphisms were found between coeliac disease patients and healthy controls. A signif…
FREQUENZA DEGLI ALLELI DEL POLIMORFISMO -330T-->G IL-2 IN UNA POPOLAZIONE DI CENTENARI ITALIANI
Cytokine Gene Polymorphisms and Breast Cancer Susceptibility
Human breast cancer (BC) is characterized by a considerable clinical heterogeneity. Steroid hormone receptor expression and growth factor receptor expression have been considered suitable diagnostic and prognostic markers, whereas mutations of oncosuppressor and gatekeeper genes have been found associated with an increased risk for this malignancy. To evaluate the role that polymorphisms of genes involved in the regulation of inflammatory response might play in BC susceptibility, we investigated associations between cytokine functionally relevant polymorphisms in 84 BC patients compared to 110 age- and sex-matched controls. TNF-alpha (-308G/A), TGF-beta1 (+869C/T), IL-10 (-1117G/A; -854C/T;…
Variazioni delle frequenze degli alleli di ApoE in soggetti anziani ed in pazienti affetti da sindrome di Down.
Analysis of IL-6, IL-10 and IL-17 genetic polymorphisms as risk factors for sepsis development in burned patients.
Abstract Infection risk, sepsis and mortality after severe burn are primarily determined by patient age, burn size, and depth. Whether genetic differences contribute to otherwise unexpected variability in outcomes is unknown. We sought to determine whether there was an association between IL-6, IL-10 and IL-17 polymorphisms with cytokine production and development of sepsis. We evaluated 71 patients with burns ≥15% TBSA and 109 healthy subjects. The genotypes of IL-6 (−174C/G), IL-10 (−819C/T and −1082A/G) and IL-17 (7488T/C) polymorphisms were identified applying polymerase chain reaction protocols. The cytokine levels in serum were determined with enzyme-linked immunoabsorbent assays. Our…
Analisi dei polimorfismi funzionali dei geni IL-10 e TNF e della produzione di citochine in pazienti affetti da Malattia di Alzheimer di tipo sporadico.
The close link between the fetal programming imprinting and neurodegeneration in adulthood: The key role of “hemogenic endothelium” programming
The research on neurodegenerative diseases (NeuroDegD) has been traditionally focused on later life stages. There is now an increasing evidence, that they may be programmed during early development. Here, we propose that NeuroDegD are the result of the complex process of imprinting on fetal hemogenic endothelium, from which the microglial cells make to origin. The central role of placenta and epigenetic mechanisms (methylation of DNA, histone modifications and regulation by non-coding RNAs) in mediating the short and long-term effects has been also described. Precisely, it reports their role in impacting plasticity and memory of microglial cells. In addition, we also underline the necessity…
Inflammation genes and Alzheimer’s disease.
IL-1 Superfamily Member (IL-1A, IL-1B and IL-18) Genetic Variants Influence Susceptibility and Clinical Course of Mediterranean Spotter Fever
Mediterranean Spotted Fever (MSF) is one of the most common spotted fever Rickettsioses. Most cases of MSF follow a benign course, with a minority of cases being fatal. The severity of the infection depends on bacterial virulence, dose and host factors such as effective immune response and genetic background. Herein, we reported data on typing by competitive allele-specific PCR of functionally relevant polymorphisms of genes coding for MyD88 adapter-like (Mal/TIRAP) protein (rs8177374), interleukin(IL)-1 cluster (IL-1A rs1800587, IL-1B rs16944 and rs1143634) and IL-18 (rs187238), which might be crucial for an efficient immune response. The results enlighten the role that IL-1 gene cluster v…
Immune-inflammatory responses in successful and unsuccessful ageing
A dramatic increase in mean life span and life expectancy, coupled with a significant reduction in early mortality, has lead to a large increase in number of elderly people in modern societies. This demographic phenomenon has been paralleled by an epidemic of chronic diseases associated with advancing age. Both innate and instructive immunity are implicated in almost all age-related diseases. The modifications of the immune system in the elderly are evaluated as a deterioration of the immune system, the so-called immunosenescence, which is thought to be mostly the result of the declining effectiveness of T cells and it is responsible for the increased susceptibility of elderly to infectious…
Analysis of functionally Relevant Single nucleotide polymorphisms of TNFα and of IFN-gamma in Celiac Disease
A genetically determined high setting of TNF-alpha influences immunologic parameters of HLA-B8,DR3 positive subjects: implications for autoimmunity.
The 8.1 ancestral haplotype (AH) is a common Caucasoid haplotype carried by most people who type for HLA-B8,DR3. It seems unique in its association with a wide range of immunopathologic diseases. Healthy subjects bearing this haplotype demonstrate several alterations of immune response. This article will focus on the identification of the mechanism(s) of disease susceptibility of 8.1 AH. In 13 carriers of 8.1 AH, and 43 negative patients, enzyme immune assays serum levels of tumor necrosis factor (TNF)-alpha, soluble endothelial leukocyte adhesion molecule-1 (sELAM-1), cortisol, and interleukin(IL)-10 were determined. In addition, quantification of cytokine produced in vitro after mitogen s…
Age at onset of Alzheimer disease and Tumor Necrosis Factor-Alpha -308A/G Polymorphism. Alzheimer’s and Parkinson diseases:
Genetics of longevity. Data from the studies on Sicilian centenarians
Abstract The demographic and social changes of the past decades have determined improvements in public health and longevity. So, the number of centenarians is increasing as a worldwide phenomenon. Scientists have focused their attention on centenarians as optimal model to address the biological mechanisms of "successful and unsuccessful ageing". They are equipped to reach the extreme limits of human life span and, most importantly, to show relatively good health, being able to perform their routine daily life and to escape fatal age-related diseases, such as cardiovascular diseases and cancer. Thus, particular attention has been centered on their genetic background and immune system. In thi…
Interleukin-5 production by mononuclear cells from aged individuals: implication for autoimmunity.
It is well known that in the elderly a deterioration of immune functions may occur. Particularly, stimulation of T cells from aged individuals leads to different kind and/or size of responses if compared with the responses obtained from T cells from young individuals. At the same time, an increase in prevalence of autoantibodies occurs in elderly. The altered production of certain cytokines might explain this paradox of decreased responsiveness to foreign antigens in the face of an increased response to self-antigens. We and others have suggested that this kind of immune response might depend on an age-associated impairment of Th-1 type function that selectively affects production of cytoki…
Helicobacter pylori and Epstein–Barr Virus Infection in Gastric Diseases: Correlation with IL-10 and IL1RN Polymorphism
Introduction. Helicobacter pylori and Epstein–Barr virus (EBV) infection have recently been shown to be associated with gastric diseases. Polymorphisms in genes encoding cytokines such as interleukin 10 (IL-10) and interleukin 1 Receptor (IL-1RN) influence cytokine secretion levels and appear to contribute to the risk of developing gastroduodenal diseases. To our knowledge, this is the first preliminary study to address the association of coinfection with H. pylori and EBV and their correlation with genetic predisposition in the development of gastric diseases. Methods. Gastric biopsy samples of 96 patients with different gastric diseases were used. Results. Our results showed that the rate…
Proposta di protocollo per la determinazione dei valori normali di riferimento per i comuni test di routine nella popolazione anziana
Polymorphism of cytochrome P450 (CYP) genes and response to chemiotherapy in patients with colorectal cancer (CRC)
Background: Genes coding for the cytochrome P450 (CYP) enzyme system implied in antineoplastic drug metabolism pathways are highly polymorphic. This may influence both carcinogen metabolism and drug pharmacodynamics modifying their therapeutic efficacy and side effects. Methods: We investigated the influence of genetic polymorphisms of CYP enzymes: rs1799853 (CYP2C9), rs35742686 (CYP2D), rs5030655 (CYP2D6/3), rs2740574 (CYP3A4/1) rs776746 (CYP3A5) on the response of chemotherapy and clinical outcomes, in a group of 56 patients affected by sporadic CRC, treated with the standard protocols. A total of 44 patients were in complete remission after treatment, 12 had persistence of the disease. P…
Characterization of two alternative Interleukin(IL)-10 5′UTR mRNA sequences, induced by lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells
Abstract IL-10 production shows a broad-spectrum of individual response, suggesting a genetic component of approximately 75%. Different polymorphisms located close to, or within the IL-10 gene has been demonstrated to influence its transcription rate whereas the post-transcriptional regulation of IL-10 production has not well elucidated. The main responsible elements at this control level are both the 5′- and 3′-untranslated regions (UTR's) of mRNAs, and as the 3′-UTR regions are mainly involved in the stability and decay rate of mRNAs, the 5′-UTR regions mediate the binding rate of the molecule with ribosomal 40S subunit as a cis-acting element. Herein are report data on the identification…
Risk profiles in type 2 diabetes (metabolic syndrome): integration of IL-10 polymorphisms and laboratory parameters to identify vascular damages related complications
Recently it has been reported that low serum IL-10 levels are associated with an increased susceptibility for metabolic syndrome and type 2 diabetes mellitus (T2DM). We investigated whether the -1087G/A (rs1800896), -824C/T (rs1800871), -597C/A (rs1800872) IL-10 polymorphisms were associated with type 2 diabetes in a study on a cohort of Italian Caucasians comprising 490 type 2 diabetic and 349 control subjects. Stratifying the data according to IL-10 genotypes, trends for the progressive increase of glucose and neutrophil levels were observed in -1087GG vs. -1087GA vs. -1087AA positive diabetic patients (-1087GG < -1087GA < -1087AA). In addition, evaluating the laboratory parameters accord…
Opposite effects of interleukin 10 common gene polymorphisms in cardiovascular diseases and in successful ageing: genetic background of male centenarians is protective against coronary heart disease
Many aspects of ageing involve inflammatory processes. We evaluated the association with longevity of alleles of IL10 and TNFa, known to have opposite functions in inflammatory reactions, IL-10 acting predominantly as an anti-inflammatory and TNF-a as a proinflammatory factor. The number of male centenarians homozygous for the –1082G genotype, suggested to be associated with high IL-10 production, was significantly increased in comparison with younger control subjects. No significant differences were observed between women and controls. The genotypic frequencies of the TNFa promoter SNPs 308G and 308A, suggested to be associated with low and high TNF-a production respectively, were not sign…
Construction of a reference panel for IGF-1 gene expression: strategies for the identification of “genetic doping” practices.
Analysis of Candidate Genes in Celiac Disease: A Tool to Identify Life-Threatening Associated Genes?
The authors have recently reported that celiac patients show a proinflammatory cytokine genetic profile characterized by the contemporaneous presence of both the tumour necrosis factor-alpha-308A and the interferon-gamma +874T allele-positive genotypes. The same alleles are considered risk factors for aging associated disease, whereas an anti-inflammatory cytokine genotype profile might be associated with an extended life expectancy. This paper reports data on the 1249-1250InsACAA/Non-Ins transforming growth factor (TGF)-beta2, a multifunctional anti-inflammatory cytokine, polymorphism distribution in 88 celiac disease (CD) patients, 99 age- and sex-matched controls, and 2895-year-old healt…
Role of TGF-β Pathway Polymorphisms in Sporadic Thoracic Aortic Aneurysm: rs900 TGF-β2 Is a Marker of Differential Gender Susceptibility
Thoracic aortic aneurysm (TAA) is a progressive disorder involving gradual dilation of ascending and/or descending thoracic aorta with dissection or rupture as complications. It occurs as sporadic or defined syndromes/familial forms.Genetic, molecular and cellular mechanims of sporadic TAA forms are poorly characterized and known. Thus, our interest has been focused on investigating the role of genetic variants of transforming growth factor-β(TGF-β) pathways in TAA risk. On the other hand, no data on the role of genetic variants of TGF-βpathway in sporadic TAA exist until now. In addition, other cytokines, including IL-10, orchestrate TAA pathophysiology. Their balance determines the ultima…
Valutazione della “gene expression” di IGF-1 ed IGF-1R in soggetti dediti ad attività sportiva: costruzione di un panel di riferimento utile all’identificazione di casi di “doping genico”
Integrated analysis of colorectal cancer microRNA datasets: Identification of microRNAs associated with tumor development
Colorectal cancer (CRC) is one of the leading cause of cancer death worldwide. Currently, no effective early diagnostic biomarkers are available for colorectal carcinoma. Therefore, there is a need to discover new molecules able to identify pre-cancerous lesions. Recently, microRNAs (miRNAs) have been associated with the onset of specific pathologies, thus the identification of miRNAs associated to colorectal cancer may be used to detect this pathology at early stages. On these bases, the expression levels of miRNAs were analyzed to compare the miRNAs expression levels of colorectal cancer samples and normal tissues in several miRNA datasets. This analysis revealed a group of 19 differentia…
TGF-β/VEGF-A Genetic Variants Interplay in Genetic Susceptibility to Non-Melanocytic Skin Cancer
Differential genetically determined expression of transforming growth factor-β (TGF-β pathway and of vascular endothelial growth factor-A (VEGF-A) might modulate the molecular “milieu” involved in the etio-pathogenesis of non-melanoma skin cancer (NMSC). We have evaluated the frequency of some functionally relevant SNPs of TGF-β and VEGF-A genes in 70 NMSC patients and 161 healthy controls, typed for TGF-β1 rs1800471, TGF-β2 rs900, TGF-βR1 rs334348 and rs334349, TGF-βR2 rs4522809 and VEGF-A rs3025039 SNPs. TGF-βR2 rs1800629G allele and related genotypes were found to be associated with a possible protective role against NMSC, whereas VEGF-…
Genotyping strategy of SMAD-3 rs3825977 gene variant for a differential management of ascending aorta aneurysm in women people: Gender oriented diagnostic tools
Abstract Background and objectives The research of opportune strategies for facilitating the management of complex pathologies, such as ascending aorta aneurysm (AAA), currently represents the principal object of clinicians, clinical pathologists included. Herein, we propose genotyping of gene variants related to TGF-β pathway as useful strategy to improve the complex AAA management, exclusively based on imaging evaluations. Precisely, we investigated four functional SNPs in SMAD and VEGF genes, encoding molecules able to modulate functions and cross-talks of TGF-β pathway. Populations and methods Our study included 92 individuals (70 men (76%) and 22 (24%) women; mean age: 71.4 ± 2.6 years…
Interleukin-12 release by mitogen-stimulated mononuclear cells in the elderly.
Abstract Defects involving cellular expression of activation molecules, cell mediated immune response and natural killer (NK) activity are commonly observed in the elderly. Herein, data are reported on the evaluation of IL-12 production by old subjects. IL-12 is, actually, considered the key molecule for the induction of a T helper 1 (Th1) -type and NK response. IL-12 production from old subjects peripheral blood mononuclear cells (PBMNC) was evaluated using T-independent (bacterial lipopolysaccharide, LPS) or -dependent (phytoemagglutinin, PHA; immobilized anti-CD3 monoclonal antibodies, anti-CD3) mitogens. The IL-12 production after LPS stimulation was not reduced in cultures from old sub…