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Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women.

ABSTRACT: DNA methylation is an epigenetic modification essential for the regulation of gene expression that has been implicated in many diseases, including cancer. Few studies have investigated the wide range of potential predictors of global DNA methylation, including biomarkers. Here, we investigated associations between DNA methylation and dietary factors, sex-steroid hormones, metabolic, lipid, inflammation, immune and one-carbon biomarkers. Data and baseline biomarker measurements were obtained from 173 overweight/obese postmenopausal women. Global DNA methylation in lymphocyte DNA was measured using the pyrosequencing assay for LINE-1 repeats. We used correlations and linear regression analyses to investigate associations between continuous data and DNA methylation, while t-tests were used for categorical data. Secondary analyses stratified by serum folate levels and multivitamin use were also conducted. There was little variability in LINE-1 methylation (66.3-79.5%). Mean LINE-1 methylation was significantly higher among women with elevated glucose levels. Mean LINE-1 methylation was also higher among women with high CD4+/CD8+ ratio, and lower among women with elevated vitamin B6, but neither reached statistical significance. In analyses stratified by folate status, DNA methylation was negatively associated with sex hormone concentrations (estrone, estradiol, testosterone and sex hormone binding globulin) among women with low serum folate levels (n = 53). Conversely, among women with high serum folate levels (n = 53), DNA methylation was positively associated with several immune markers (CD4/CD8 ratio, NK1656/lymphocytes and IgA). Results from this screening suggest that global DNA methylation is generally stable, with differential associations for sex hormones and immune markers depending on one-carbon status.

SUBMITTER: Ulrich CM

PROVIDER: S-EPMC3515011 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women.

Ulrich Cornelia M CM Toriola Adetunji T AT Koepl Lisel M LM Sandifer Tracy T Poole Elizabeth M EM Duggan Catherine C McTiernan Anne A Issa Jean-Pierre J JP

Epigenetics 20120807 9

DNA methylation is an epigenetic modification essential for the regulation of gene expression that has been implicated in many diseases, including cancer. Few studies have investigated the wide range of potential predictors of global DNA methylation, including biomarkers. Here, we investigated associations between DNA methylation and dietary factors, sex-steroid hormones, metabolic, lipid, inflammation, immune and one-carbon biomarkers. Data and baseline biomarker measurements were obtained from ...[more]

PMID: 22869041

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Project description:BackgroundMetabolic risk varies according to body mass index (BMI), body fat distribution and ethnicity. In recent years, epigenetics, which reflect gene-environment interactions have attracted considerable interest as mechanisms that may mediate differences in metabolic risk. The aim of this study was to investigate DNA methylation differences in abdominal and gluteal subcutaneous adipose tissues of normal-weight and obese black and white South African women.MethodsBody composition was assessed using dual-energy x-ray absorptiometry and computerized tomography, and insulin sensitivity was measured using a frequently sampled intravenous glucose tolerance test in 54 normal-weight (BMI 18-25 kg/m2) and obese (BMI ≥ 30 kg/m2) women. Global and insulin receptor (INSR) DNA methylation was quantified in abdominal (ASAT) and gluteal (GSAT) subcutaneous adipose depots, using the Imprint methylation enzyme-linked immunosorbent assay and pyrosequencing. INSR gene expression was measured using quantitative real-time PCR.ResultsGlobal DNA methylation in GSAT varied according to BMI and ethnicity, with higher levels observed in normal-weight white compared to normal-weight black (p = 0.030) and obese white (p = 0.012) women. Pyrosequencing of 14 CpG sites within the INSR promoter also showed BMI, adipose depot and ethnic differences, although inter-individual variability prevented attainment of statistical significance. Both global and INSR methylation were correlated with body fat distribution, insulin resistance and systemic inflammation, which were dependent on ethnicity and the adipose depot. Adipose depot and ethnic differences in INSR gene expression were observed.ConclusionWe show small, but significant global and INSR promoter DNA methylation differences in GSAT and ASAT of normal-weight and obese black and white South African women. DNA methylation in ASAT was associated with centralization of body fat in white women, whereas in black women DNA methylation in GSAT was associated with insulin resistance and systemic inflammation. Our findings suggest that GSAT rather than ASAT may be a determinant of metabolic risk in black women and provide novel evidence that altered DNA methylation within adipose depots may contribute to ethnic differences in body fat distribution and cardiometabolic risk.

Project description:Much has been claimed on the health benefits of alkaline water including metabolic syndrome (MetS) and its features with scarcity of scientific evidence. Methods: This cross-sectional comparative study was conducted to determine whether regular consumption of alkaline water confers health advantage on blood metabolites, anthropometric measures, sleep quality and muscle strength among postmenopausal women. A total of 304 community-dwelling postmenopausal women were recruited with comparable proportion of regular drinkers of alkaline water and non-drinkers. Participants were ascertained on dietary intake, lifestyle factors, anthropometric and biochemical measurements. Diagnosis of MetS was made according to Joint Interim Statement definition. A total of 47.7% of the participants met MS criteria, with a significant lower proportion of MetS among the alkaline water drinkers. The observed lower fasting plasma glucose (F(1,294) = 24.20, p = 0.025, partial η2 = 0.435), triglyceride/high-density lipoprotein concentration ratio (F(1,294) = 21.06, p = 0.023, partial η2 = 0.360), diastolic blood pressure (F(1,294) = 7.85, p = 0.046, partial η2 = 0.258) and waist circumference (F(1,294) = 9.261, p = 0.038, partial η2 = 0.263) in the alkaline water drinkers could be considered as favourable outcomes of regular consumption of alkaline water. In addition, water alkalization improved duration of sleep (F(1,294) = 32.05, p = 0.007, partial η2 = 0.451) and handgrip strength F(1,294) = 27.51, p = 0.011, partial η2 = 0.448). Low density lipoprotein cholesterol concentration (F(1,294) = 1.772, p = 0.287, partial η2 = 0.014), body weight (F(1,294) = 1.985, p = 0.145, partial η2 = 0.013) and systolic blood pressure (F(1,294) = 1.656, p = 0.301, partial η2 = 0.010) were comparable between the two different water drinking behaviours. In conclusion, drinking adequate of water is paramount for public health with access to good quality drinking water remains a critical issue. While consumption of alkaline water may be considered as a source of easy-to implement lifestyle to modulate metabolic features, sleep duration and muscle strength, further studies are warranted for unravelling the precise mechanism of alkaline water consumption on the improvement and prevention of MetS and its individual features, muscle strength and sleep duration as well as identification of full spectrum of individuals that could benefit from its consumption.

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Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women.

Publications

Metabolic, hormonal and immunological associations with global DNA methylation among postmenopausal women.

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