Search results for "Predisposition"
showing 10 items of 771 documents
Genetic influences on adult body mass index followed over 29 years and their effects on late-life mobility: a study of twin sisters.
2009
Background: The rise in body mass index (BMI) during adulthood increases the risk for metabolic disorders, functional limitations and disability in old age. This twin study examined prospectively whether genetic and environmental influences on women’s BMI also account for mobility 29 years later. Methods: The sample consisted of 103 monozygotic and 114 dizygotic pairs of twin sisters reared together. Body mass index was initially evaluated in 1975, when the women were aged 42.6±3.4 years, and was followed-up in 1981, 1990, 2001 and 2004. Mobility was evaluated using the standardised 6-minute walking test in 2001, when the women were aged 68.6±3.2 years, and followed-up 3 years later. An inv…
Effect of physical activity on health in twins: a 30-yr longitudinal study.
2010
Purpose: The aim of this study was to investigate whether persistent leisure-time physical activity, adjusted for genetic liability and childhood experiences, protects against chronic diseases, early signs of disability, and loss of life satisfaction. Methods: From 5663 healthy adult twin pairs, we identified 146 pairs who were discordant for both intensity and volume of leisure physical activity in 1975 and 1981. Of them, both members of 95 pairs were alive and participated in our follow-up study in 2005 when chronic diseases (such as diabetes, cardiovascular disease, and osteoarthritis), life satisfaction, and disability were assessed by a structured telephone interview. The mean age of t…
Epidemiology of Disease Conditions in Italy. Has Anything Changed? Environment, Professional Exposure, and Lifestyle. Is Time for Screening?
2013
Risk factors analysis in bladder cancer should consider not only the clinical and pathological features of the tumor but also environmental and lifestyle factors. They may play, in fact, a relevant role not only in the pathogenesis but also in the biological behavior of the tumor. The association between cigarette smoking and bladder cancer has been consistently confirmed in several case-control and cohort studies. The risk of bladder cancer seems to increase with duration and intensity of smoking. Another environmental risk factor, although not definitively proved, is water supply. Chlorination or water pollution by pesticides and other chemical factors is considered a relevant risk facto…
Co-factors, Microbes, and Immunogenetics in Celiac Disease to Guide Novel Approaches for Diagnosis and Treatment.
2021
Celiac disease (CeD) is a frequent immune-mediated disease that affects not only the small intestine but also many extraintestinal sites. The role of gluten proteins as dietary triggers, HLA-DQ2 or -DQ8 as major necessary genetic predisposition, and tissue transglutaminase (TG2) as mechanistically involved autoantigen, are unique features of CeD. Recent research implicates many cofactors working in synergism with these key triggers, including the intestinal microbiota and their metabolites, nongluten dietary triggers, intestinal barrier defects, novel immune cell phenotypes, and mediators and cytokines. In addition, apart from HLA-DQ2 and -DQ8, multiple and complex predisposing genetic fact…
Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis
2021
Key Points Question What genetic variants are associated with juvenile amyotrophic lateral sclerosis (ALS)? Findings In this family-based genetic study, exome sequencing was performed in 3 patients diagnosed with juvenile ALS and failure to thrive; this identified de novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient). Variants in SPTLC1 are a known cause of hereditary sensory and autonomic neuropathy, type 1A, and these data extend the phenotype associated with this gene. Meaning De novo variants in the SPTLC1 gene are associated with juvenile ALS, a fatal neurological disorder.
Pharmacokinetic properties of recombinant FVIIa in inherited FVII deficiency account for a large volume of distribution at steady state and a prolong…
2014
Pharmacokinetic properties of recombinant FVIIa in inherited FVII deficiency account for a large volume of distribution at steady state and a prolonged pharmacodynamic effect -
Effects of BRCA2 cis-regulation in normal breast and cancer risk amongst BRCA2 mutation carriers
2012
Introduction: Cis-acting regulatory single nucleotide polymorphisms (SNPs) at specific loci may modulate penetrance of germline mutations at the same loci by introducing different levels of expression of the wild-type allele. We have previously reported that BRCA2 shows differential allelic expression and we hypothesize that the known variable penetrance of BRCA2 mutations might be associated with this mechanism. Methods: We combined haplotype analysis and differential allelic expression of BRCA2 in breast tissue to identify expression haplotypes and candidate cis-regulatory variants. These candidate variants underwent selection based on in silico predictions for regulatory potential and di…
Genetic Determined Downregulation of Both Type 1 and Type 2 Cytokine Pathways Might Be Protective against Pancreatic Cancer
2009
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…
Genetics: GWAS identifies 24 new loci for renal function.
2016
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation o…
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
2011
Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have ena…