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Differential DNA Methylation in Relation to Age and Health Risks of Obesity.

ABSTRACT: The aim of this study was to evaluate whether genome-wide levels of DNA methylation are associated with age and the health risks of obesity (HRO); defined according to BMI categories as "Low HRO" (overweight and class 1 obesity) versus "High HRO" (class 2 and class 3 obesity). Anthropometric measurements were assessed in a subsample of 48 volunteers from the Metabolic Syndrome Reduction in Navarra (RESMENA) study and 24 women from another independent study, Effects of Lipoic Acid and Eicosapentaenoic Acid in Human Obesity (OBEPALIP study). In the pooled population; the methylation levels of 55 CpG sites were significantly associated with age after Benjamini-Hochberg correction. In addition, DNA methylation of three CpG sites located in ELOVL2; HOXC4 and PI4KB were further negatively associated with their mRNA levels. Although no differentially methylated CpG sites were identified in relation to HRO after multiple testing correction; several nominally significant CpG sites were identified in genes related to insulin signaling; energy and lipid metabolism. Moreover, statistically significant associations between BMI or mRNA levels and two HRO-related CpG sites located in GPR133 and ITGB5 are reported. As a conclusion, these findings from two Spanish cohorts add knowledge about the important role of DNA methylation in the age-related regulation of gene expression. In addition; a relevant influence of age on DNA methylation in white blood cells was found, as well as, on a trend level, novel associations between DNA methylation and obesity.

SUBMITTER: Mansego ML

PROVIDER: S-EPMC4581172 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Differential DNA Methylation in Relation to Age and Health Risks of Obesity.

Mansego María Luisa ML Milagro Fermín I FI Zulet María Ángeles MÁ Moreno-Aliaga María J MJ Martínez José Alfredo JA

International journal of molecular sciences 20150724 8

The aim of this study was to evaluate whether genome-wide levels of DNA methylation are associated with age and the health risks of obesity (HRO); defined according to BMI categories as "Low HRO" (overweight and class 1 obesity) versus "High HRO" (class 2 and class 3 obesity). Anthropometric measurements were assessed in a subsample of 48 volunteers from the Metabolic Syndrome Reduction in Navarra (RESMENA) study and 24 women from another independent study, Effects of Lipoic Acid and Eicosapenta ...[more]

PMID: 26213922

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Project description:Background: The brain atrophy and lesion index (BALI) has been developed to assess whole-brain structural deficits that are commonly seen on magnetic resonance imaging (MRI) in aging. It is unclear whether such changes can be detected at younger ages and how they might relate to other exposures. Here, we investigate how BALI scores, and the subcategories that make the total score, compare across adulthood and whether they are related to the level of cardiovascular risks, in both young and old adulthood. Methods: Data were from 229 subjects (72% men; 24-80 years of age) whose annual health evaluation included a routine anatomical MRI examination. A BALI score was generated for each subject from T2-weighted MRI. Differences in the BALI total score and categorical subscores were examined by age and by the level of cardiovascular risk factors (CVRFs). Regression analysis was used to evaluate relationships between continuous variables. Relative risk ratios (RRRs) of CVRF on BALI were examined using a multinomial logistic regression. The area under the receiver operating characteristic (ROC) curve was used to estimate the classification accuracy. Results: Nearly 90% of the participants had at least one CVRF. Mean CVRF scores increased with age (slope = 0.03; r = 0.36, 95% confidence intervals: 0.23-0.48; p < 0.001). The BALI total score was closely related to age (slope = 0.18; r = 0.69, 95% confidence intervals: 0.59-0.78; p < 0.001), as so were the categorical subscores (r's = 0.41-0.61, p < 0.001); each differed by the number of CVRF (t-test: 4.16-14.83, χ 2: 6.9-43.9, p's < 0.050). Multivariate analyses adjusted for age and sex suggested an independent impact of age and the CVRF on the BALI score (for each year of advanced age, RRR = 1.20, 95% CI = 1.11-1.29; for each additional CVRF, RRR = 3.63, 95% CI = 2.12-6.23). The CVRF and BALI association remained significant even in younger adults. Conclusion: The accumulation of MRI-detectable structural brain deficits can be evident from young adulthood. Age and the number of CVFR are independently associated with BALI score. Further research is needed to understand the extent to which other age-related health deficits can increase the risk of abnormalities in brain structure and function, and how these, with BALI scores, relate to cognition.

Dataset Information

Differential DNA Methylation in Relation to Age and Health Risks of Obesity.

Publications

Differential DNA Methylation in Relation to Age and Health Risks of Obesity.

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