期刊
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
卷 41, 期 1, 页码 126-139出版社
OXFORD UNIV PRESS
DOI: 10.1093/ije/dyq154
关键词
Blood; DNA methylation; epigenetics; meta-analysis; repetitive elements
资金
- National Institute of Environmental Health Sciences [ES015172-01]
- Environmental Protection Agency [R83241601, R827353]
- Cooperative Studies Program/Epidemiology Research and Information Center of the U. S. Department of Veterans Affairs
- Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC)
- Intramural Research Program (Division of Cancer Epidemiology and Genetics, NCI) of the National Institutes of Health
- Diane Belfer Program for Human Microbial Diversity
- National Institutes of Health [R01GM63270]
- Italian Association for Cancer Research (AIRC) [(2008-10) [6016]]
- Cariplo Foundation [2007-5469]
- Italian Ministry of Scientific Research (MIUR) [PRIN-20072S2HT8]
- Milan University
Background Estimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals. Methods Individual data from five studies including a total of 1465 healthy subjects were combined. DNA methylation was quantified by PCR-pyrosequencing. Results Age [beta = -0.011% of 5-methyl-cytosine (% 5mC)/year, 95% confidence interval (CI) -0.020 to -0.001% 5mC/year] and alcohol drinking (beta = -0.214, 95% CI -0.415 to -0.013) were inversely associated with Alu methylation. Compared with females, males had lower Alu methylation (beta = -0.385, 95% CI -0.665 to -0.104) and higher LINE-1 methylation (-0.796, 95% CI 0.261 to 1.330). No associations were found with smoking or BMI. Percent neutrophils and lymphocytes in blood counts exhibited a positive (beta=0.036, 95% CI 0.010 to 0.061) and negative (beta = -0.038, 95% CI -0.065 to -0.012) association with LINE-1 methylation, respectively. Conclusions Global methylation measures in blood DNA vary in relation with certain host and lifestyle characteristics, including age, gender, alcohol drinking and white blood cell counts. These findings need to be considered in designing epidemiological investigations aimed at identifying associations between DNA methylation and health outcomes.
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