Search results for "Predisposition"
showing 10 items of 771 documents
TLR4 polymorphisms and ageing: implications for the pathophysiology of age-related diseases.
2009
Innate immunity provides a first line of host defense against infection by recognizing and killing microbes while simultaneously activating an instructive immune response. Toll-like receptors (TLRs) are principal mediators of rapid microbial recognition and function mainly by detection of pathogen-associated molecular patterns that do not exist in the host. Recognition of their ligands leads to a series of signaling events resulting in acute host responses, involved in killing pathogens. Discussion We describe the involvement of TLR4 polymorphisms in ageing, and in particular in age-related diseases, suggesting the crucial role of molecules of innate immunity in pathophysiology of these dis…
Event-related potentials in newborns with and without familial risk for dyslexia: principal component analysis reveals differences between the groups
2003
Differences revealed by factor scores extracted by principal component analysis (PCA) from event-related potential (ERP) data of newborns with and without familial risk for dyslexia were examined and compared to results obtained by using original averaged ERPs. ERPs to consonant-vowel syllables (synthetic /ba/, /da/, /ga/; and natural /paa/, /taa/, /kaa/) were recorded from 26 at-risk and 23 control 1-7 day-old infants. The stimuli were presented equiprobably and with interstimulus intervals varying at random from 3,910 to 7,285 ms. Statistically significant between-group differences were found to be relatively similar irrespective of the methods of analysis (original ERPs vs. factor scores…
Mutations in the HFE gene and cardiovascular disease risk: an individual patient data meta-analysis of 53 880 subjects.
2008
Background— Whether mutations in the hemochromatosis (HFE) gene increase cardiovascular disease risk is still undetermined. The main reason is the low frequency of the mutations, in particular of the compound C282Y/H63D genotype. We combined the data of 11 observational studies for an individual patient data meta-analysis. Methods and Results— Individual patient data were obtained from published as well as unpublished studies that had information available on the C282Y mutation as well as the H63D mutation in relation to coronary heart disease risk. Individual records were provided on each of the 53 880 participants in 11 studies. In total, 10 541 patients with coronary events were documen…
Frailty and Risk of Cardiovascular Diseases in Older Persons: The Age, Gene/Environment Susceptibility-Reykjavik Study
2017
Frailty is a risk factor for cardiovascular diseases (CVD), but the studies available have not considered the presence of subclinical atherosclerotic disease as potential confounders. We investigated the association between frailty and the onset of CVD independently of subclinical atherosclerotic disease. For this reason, a sample of 3818 older participants participating in the Age, Gene/Environment Susceptibility-Reykjavik Study without CVD at baseline was followed for a median of 8.7 years. Frailty was defined as the presence of ≥3 among five Fried's criteria (unintentional weight loss, low physical activity level, weakness, exhaustion, and slow gait speed). Incident CVD was defined as on…
Late-onset myasthenia gravis - CTLA4(low) genotype association and low-for-age thymic output of naïve T cells.
2014
Abstract Late-onset myasthenia gravis (LOMG) has become the largest MG subgroup, but the underlying pathogenetic mechanisms remain mysterious. Among the few etiological clues are the almost unique serologic parallels between LOMG and thymoma-associated MG (TAMG), notably autoantibodies against acetylcholine receptors, titin, ryanodine receptor, type I interferons or IL-12. This is why we checked LOMG patients for two further peculiar features of TAMG – its associations with the CTLA4 high/gain-of-function +49A/A genotype and with increased thymic export of naive T cells into the blood, possibly after defective negative selection in AIRE-deficient thymomas. We analyzed genomic DNA from 116 …
ITPA deficiency and ribavirin level are still predictive of anaemia in HCV–HIV-coinfected patients receiving ribavirin combined with a first-generati…
2017
Background We aimed to determine the impact of inosine triphosphatase (ITPA) deficiency on ribavirin (RBV)-induced anaemia in HIV–HCV-coinfected patients receiving a triple therapy including the haematotoxic direct-acting antiviral agent boceprevir (BOC). Methods Patients of the ANRS HC27 BocepreVIH study were genotyped for two ITPA single nucleotide polymorphisms involved in ITPA deficiency. RBV trough concentration (Ctrough) was determined at week (W)4 and W8. Impact of ITPA deficiency on anaemia, RBV Ctrough, response and haematotoxicity (grade 3/4 anaemia, erythropoietin [EPO] use, RBV dose reduction or transfusion between day [D]0 and W8) was evaluated. Impact of RBV Ctrough on anaemia…
Polymorphism in the peroxisome proliferator-activated receptor ? gene influences the risk for Alzheimer?s disease
2003
The peroxisome proliferator-activated receptor alpha (PPAR-alpha) is a member of the steroid hormone super family of ligand-inducible transcription factors, involved in glucose and lipid metabolism. We screened for polymorphisms in the PPAR-alpha gene and detected two known polymorphisms located in exon 5 and intron 7. These polymorphisms were investigated for their possible association with Alzheimer's disease (AD) and for their effect in carriers of an insulin gene (INS) polymorphism. The PPAR-alpha C --G polymorphism in exon 5 (L162V) was associated with AD, in that the V-allele was more frequent in AD patients than in healthy subjects. Further data analysis revealed that carriers of an …
Interleukin-6 gene polymorphism is an age-dependent risk factor for myocardial infarction in men.
2005
Summary Several studies show that inflammatory components may contribute to atherosclerosis and increase the risk for myocardial infarction (MI). Interleukin-6 (IL-6) is a key pro-inflammatory and immune-modulatory cytokine of relevance for cardiovascular diseases. In this case-control study, 200 patients with MI and 257 healthy controls were genotyped for the polymorphism present in −174 promoter region of the IL-6 gene. Plasma concentrations of IL-6 and C-reactive protein (CRP) in a group of patients and controls were measured. The −174 C allele was associated with an increased risk of developing MI (OR = 2.886, c.i. = 1.801–4.624, P = 0.0001) in older patients, while no association was f…
Genetic deficiency of tartrate-resistant acid phosphatase associated with skeletal dysplasia, cerebral calcifications and autoimmunity
2010
Vertebral and metaphyseal dysplasia, spasticity with cerebral calcifications, and strong predisposition to autoimmune diseases are the hallmarks of the genetic disorder spondyloenchondrodysplasia. We mapped a locus in five consanguineous families to chromosome 19p13 and identified mutations in ACP5, which encodes tartrate-resistant phosphatase (TRAP), in 14 affected individuals and showed that these mutations abolish enzyme function in the serum and cells of affected individuals. Phosphorylated osteopontin, a protein involved in bone reabsorption and in immune regulation, accumulates in serum, urine and cells cultured from TRAP-deficient individuals. Case-derived dendritic cells exhibit an …
Arylesterase Activity and Antioxidant Status Depend on PON1-Q192R and PON1-L55M Polymorphisms in Subjects with Increased Risk of Cardiovascular Disea…
2007
Human paraoxonase (PON1) exists in 2 major polymorphic forms and has been shown to protect LDL and HDL against oxidation. The aim of this study was to assess the differences between subjects at increased risk of cardiovascular disease (CVD), taking into account the effects of PON1-Q192R and PON1-L55M polymorphisms on 1) basal serum arylesterase activity, lipid peroxidation (LPO), and LDL-cholesterol (LDL-C), HDL-C, total cholesterol (TC), and oxidized-LDL (ox-LDL) concentrations; 2) the relations between arylesterase activity and lipid variables; and 3) the effect of walnut-enriched meat (WM) consumption on arylesterase activity and lipid variables. Twenty-three Caucasians at increased risk…