Search results for "Disease susceptibility"
showing 10 items of 145 documents
Search for genetic factors associated with susceptibility to multiple sclerosis.
2006
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 …
Developing the "next generation" of genetic association databases for complex diseases
2012
Tens of thousands of genetic association studies investigating the influence of common polymorphisms on disease susceptibility have been published to date. These include similar to 1,000 genome-wide association studies (GWAS). This vast amount of data in the field of complex genetics is becoming increasingly difficult to follow and interpret. It can be expected that the situation will become even more complex with the advent of association projects using next-generation technologies. One of the aims of the Human Variome Project is to concatenate such data in meaningful ways, for example, within the context of publicly available field synopses. Here, we present various examples of online gen…
The Role of Osteoprotegerin and Its Ligands in Vascular Function
2019
International audience; The superfamily of tumor necrosis factor (TNF) receptors includes osteoprotegerin (OPG) and its ligands, which are receptor activators of nuclear factor kappa-B ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). The OPG/RANKL/RANK system plays an active role in pathological angiogenesis and inflammation as well as cell survival. It has been demonstrated that there is crosstalk between endothelial cells and osteoblasts during osteogenesis, thus establishing a connection between angiogenesis and osteogenesis. This OPG/RANKL/RANK/TRAIL system acts on specific cell surface receptors, which are then able to transmit their signals to other intracellular comp…
The Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis
2020
Summary: Hypoxia-inducible factor-1 alpha (HIF-1α) is considered a global regulator of cellular metabolism and innate immune cell functions. Intracellular pathogens such as Leishmania have been reported to manipulate host cell metabolism. Herein, we demonstrate that myeloid cells from myeloid-restricted HIF-1α-deficient mice and individuals with loss-of-function HIF1A gene polymorphisms are more susceptible to L. donovani infection through increased lipogenesis. Absence of HIF-1α leads to a defect in BNIP3 expression, resulting in the activation of mTOR and nuclear translocation of SREBP-1c. We observed the induction of lipogenic gene transcripts, such as FASN, and lipid accumulation in inf…
Dystrophin-deficiency increases the susceptibility to doxorubicin-induced cardiotoxicity
2007
Background and aim: The clinical use of doxorubicin (DOX) and other anthracyclines is limited by a dosage-dependent cardiotoxicity, which can lead to cardiomyopathy. The role of the individual genetic makeup in this disorder is poorly understood. Alterations in genes encoding cardiac cytoskeleton or sarcolemma proteins may increase the susceptibility to doxorubicin-related cardiotoxicity. Methods: Female dystrophin-deficient mice (MDX) and age-matched wild-type mice underwent chronic treatment with doxorubicin. Cardiac function and tissue damage were assessed by echocardiography and histopathology, respectively. Gene expression changes were investigated using microarrays. Results: DOX treat…
Suicide and Ambient Temperature: A Multi-Country Multi-City Study
2019
Background: Previous literature suggests that higher ambient temperature may play a role in increasing the risk of suicide. However, no multi-country study has explored the shape of the association and the role of moderate and extreme heat across different locations. Objectives: We examined the short-term temperature–suicide relationship using daily time-series data collected for 341 locations in 12 countries for periods ranging from 4 to 40 y. Methods: We conducted a two-stage meta-analysis. First, we performed location-specific time-stratified case-crossover analyses to examine the temperature–suicide association for each location. Then, we used a multivariate meta-regression to combine t…
Genetic Determinants in a Critical Domain of NS5A Correlate with Hepatocellular Carcinoma in Cirrhotic Patients Infected with HCV Genotype 1b
2021
HCV is an important cause of hepatocellular carcinoma (HCC). HCV NS5A domain-1 interacts with cellular proteins inducing pro-oncogenic pathways. Thus, we explore genetic variations in NS5A domain-1 and their association with HCC, by analyzing 188 NS5A sequences from HCV genotype-1b infected DAA-naïve cirrhotic patients: 34 with HCC and 154 without HCC. Specific NS5A mutations significantly correlate with HCC: S3T (8.8% vs. 1.3%, p = 0.01), T122M (8.8% vs. 0.0%, p <
Bndocrinopathic Constitutions and Pathology of War*
1919
The clinical study of the internal secretions opens a vast field of research, so far little known, notwithstanding its great value in practical medicine. Particularly important are those states of hormonic imbalance which are at the border line between health and disease, and which represent either latent or mild endocrinopathic conditions, real endocrine diatheses or endocrinopathic temperaments. It is already understood that for each of the best known endocrine glands, in addition to frank malfunctions there must be recognized minor degrees of perturbation giving rise to the endocrinopathic habitus. To the French writers, especially Levi and Rotschild, we owe much of our knowledge of the …
Cutting Edge: IL-23 Cross-Regulates IL-12 Production in T Cell-Dependent Experimental Colitis
2006
Abstract Although IL-12 and IL-23 share the common p40 subunit, IL-23, rather than IL-12, seems to drive the pathogenesis of experimental autoimmune encephalomyelitis and arthritis, because IL-23/p19 knockout mice are protected from disease. In contrast, we describe in this study that newly created LacZ knockin mice deficient for IL-23 p19 were highly susceptible for the development of experimental T cell-mediated TNBS colitis and showed even more severe colitis than wild-type mice by endoscopic and histologic criteria. Subsequent studies revealed that dendritic cells from p19-deficient mice produce elevated levels of IL-12, and that IL-23 down-regulates IL-12 expression upon TLR ligation. …
The magnesium global network (MaGNet) to promote research on magnesium in diseases focusing on covid-19
2021
When the current SARS-CoV-2 pandemic began in early 2020, the global magnesium researcher community came together and noted the striking similarities between COVID-19 risk factors and conditions associated with magnesium deficit state in humans, reasoning that magnesium deficiency could worsen the course of COVID-19 [1-4]. This prompted establishment of a worldwide collaborative network with regular virtual meetings to brainstorm the associations between magnesium and COVID-19. We hypothesize that magnesium deficiency, a common but mostly unrecognized state in modern global societies, could be an important component of the susceptibility to SARS-CoV-2 infection. Consequently, restoring the …