Search results for " methylation"
showing 10 items of 457 documents
P16INK4A and p15INK4B gene alteration associated with oxidative stress in renal cell carcinomas after the chernobyl accident (pilot study).
2002
Our study was undertaken to better understand the role of G1/S transition abnormalities in the malignant progression of renal cell carcinomas (RCCs), exposed to long-term low doses of ionizing radiation (IR), from patients living in radiocontaminated areas of the Ukraine after the Chernobyl accident. We studied p16 and p15 gene alteration in association with oxidative stress markers, including inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2). We analyzed 88 samples collected from 22 patients with RCCs and with different exposure to IR. Homozygous deletion of the p16 and p15 genes, as well as hypermethylation of the 5CpG island in the promoter region of the same genes, were…
Sleep disturbances in Angelman syndrome: a questionnaire study.
2003
Only few studies are available on sleep disorders in Angelman syndrome (AS), a neurodevelopmental disorder with several behavior disturbances. The aim of this study was to determine the prevalence of sleep disorders in a relatively large group of AS subjects, compared to that of age-matched controls. Forty-nine consecutive parents of patients with AS (26 males and 23 females aged 2.3-26.2 years) were interviewed and filled out a comprehensive sleep questionnaire. Based on their genetic etiology, four groups were defined: deletion of chromosome 15q11-13 (25 subjects); methylation imprinting mutation (six subjects), UBE3A mutations (seven subjects) and paternal uniparental disomy (five subjec…
Identification of Epigenetic Methylation Signatures With Clinical Value in Crohn's Disease.
2019
INTRODUCTION: DNA methylation is an epigenetic mechanism that regulates gene expression and represents an important link between genotype, environment, and disease. It is a reversible and inheritable mechanism that could offer treatment targets. We aimed to assess the methylation changes on specific genes previously associated with Crohn's disease (CD) and to study their possible associations with the pathology. METHODS: We included 103 participants and grouped them into 2 cohorts (a first [n = 31] and a second validation [n = 72] cohort), with active CD (aCD) and inactive CD (iCD) and healthy participants (CTR). DNA was obtained from the peripheral blood and analyzed by the Agena platform.…
Do Epigenetic Clocks Provide Explanations for Sex Differences in Life Span? A Cross-Sectional Twin Study
2022
Abstract Background The sex gap in life expectancy has been narrowing in Finland over the past 4–5 decades; however, on average, women still live longer than men. Epigenetic clocks are markers for biological aging which predict life span. In this study, we examined the mediating role of lifestyle factors on the association between sex and biological aging in younger and older adults. Methods Our sample consists of younger and older twins (21‒42 years, n = 1 477; 50‒76 years, n = 763) including 151 complete younger opposite-sex twin pairs (21‒30 years). Blood-based DNA methylation was used to compute epigenetic age acceleration by 4 epigenetic clocks as a measure of biological aging. Path mo…
Epigenetic differences arise during the lifetime of monozygotic twins.
2005
Monozygous twins share a common genotype. However, most monozygotic twin pairs are not identical; several types of phenotypic discordance may be observed, such as differences in susceptibilities to disease and a wide range of anthropomorphic features. There are several possible explanations for these observations, but one is the existence of epigenetic differences. To address this issue, we examined the global and locus-specific differences in DNA methylation and histone acetylation of a large cohort of monozygotic twins. We found that, although twins are epigenetically indistinguishable during the early years of life, older monozygous twins exhibited remarkable differences in their overall…
BRCA1 promoter methylation in peripheral blood is associated with the risk of triple‐negative breast cancer
2019
Methylation of the promoter of the BRCA1 gene in DNA derived from peripheral blood cells is a possible risk factor for breast cancer. It is not clear if this association is restricted to certain types of breast cancer or is a general phenomenon. We evaluated BRCA1 methylation status in peripheral blood cells from 942 breast cancer patients and from 500 controls. We also assessed methylation status in 262 paraffin‐embedded breast cancer tissues. Methylation status was assessed using methylation‐sensitive high‐resolution melting and was categorized as positive or negative. BRCA1 methylation in peripheral blood cells was strongly associated with the risk of triple‐negative breast cancer (TNBC)…
Genome-wide association studies identify 137 loci for DNA methylation biomarkers of ageing
2020
AbstractBiological ageing estimators derived from DNA methylation (DNAm) data are heritable and correlate with morbidity and mortality. Leveraging DNAm and SNP data from >41,000 individuals, we identify 137 genome-wide significant loci (113 novel) from meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We report strong genetic correlations with longevity and lifestyle factors such as smoking, education, and obesity. Significant associations are observed in polygenic risk score analysis and to a lesser extent in Mendelian randomization analyses. This study illuminates the genetic …
Aging Negatively Affects Estrogens-Mediated Effects on Nitric Oxide Bioavailability by Shifting ERα/ERβ Balance in Female Mice
2011
AIMS: Aging is among the major causes for the lack of cardiovascular protection by estrogen (E2) during postmenopause. Our study aims to determine the mechanisms whereby aging changes E2 effects on nitric oxide (NO) production in a mouse model of accelerated senescence (SAM). METHODS AND RESULTS: Although we found no differences on NO production in females SAM prone (SAMP, aged) compared to SAM resistant (SAMR, young), by either DAF-2 fluorescence or plasmatic nitrite/nitrate (NO2/NO3), in both cases, E2 treatment increased NO production in SAMR but had no effect in SAMP. Those results are in agreement with changes of eNOS protein and gene expression. E2 up-regulated eNOS expression in SAMR…
Implementing Precision Medicine in Human Frailty through Epigenetic Biomarkers
2021
The main epigenetic features in aging are: reduced bulk levels of core histones, altered pattern of histone post-translational modifications, changes in the pattern of DNA methylation, replacement of canonical histones with histone variants, and altered expression of non-coding RNA. The identification of epigenetic mechanisms may contribute to the early detection of age-associated subclinical changes or deficits at the molecular and/or cellular level, to predict the development of frailty, or even more interestingly, to improve health trajectories in older adults. Frailty reflects a state of increased vulnerability to stressors as a result of decreased physiologic reserves, and even dysregu…
Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging
2021
Abstract Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci ass…