期刊
EPIGENOMICS
卷 9, 期 12, 页码 -出版社
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2017-0094
关键词
AGO2; air pollution; epigenetic aging; miRNA; PM2.5; SNPs
资金
- National Institute of Environmental Health Sciences (NIEHS) [R01ES021733, R01ES025225]
- NIEHS [ES015172, ES014663, ES020010, P30ES009089, P30ES000002]
- Environmental Protection Agency [RD832416, RD83587201]
- National Heart, Lung, and Blood Institute [2T32HL007118-41]
- US Department of Agriculture, Agricultural Research Service [53-K06-510]
- Cooperative Studies Program/ERIC, US Department of Veterans Affairs
- NIH/NIA Ruth L Kirschstein National Research Service Award [1 F31AG056124-01A1]
We tested whether genetic variation in miRNA processing genes modified the association of PM2.5 with DNA methylation (DNAm) age. Patients & methods: We conducted a repeated measures study based on 552 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n = 940 visits). Address-level 1-year PM2.5 exposures were estimated using the GEOS-chem model. DNAm-age and a panel of 14 SNPs in miRNA processing genes were measured from participant blood samples. Results & conclusion: In fully adjusted linear mixed-effects models, having at least one copy of the minor rs4961280 [AGO2] allele was associated with a lower DNAm-age (beta = -1.13; 95% CI: -2.26 to -0.002). However, the association of PM2.5 with DNAm-age was significantly (P-interaction = 0.01) weaker in homozygous carriers of the major rs4961280 [AGO2] allele (beta = 0.38; 95% CI: -0.20 to 0.96) when compared with all other participants (beta = 1.58; 95% CI: 0.76 to 2.39). Our results suggest that miRNA processing impacts DNAmage relationships. Graphical abstract: miRNA processing AGO2 polymorphism (rs4961280) modifies the association of long-term ambient fine particle exposure with blood DNA methylation age [GRAPHICS] The graph depicts lines from a fully adjusted linear regression model with fine particle exposure levels ranging from the tenth to the ninetieth percentile, all other continuous variables held constant at their means, and all other categorical variables held at their most frequent level.
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