Format

Send to

Choose Destination
Epigenomics. 2017 Dec;9(12):1529-1542. doi: 10.2217/epi-2017-0094. Epub 2017 Nov 6.

miRNA processing gene polymorphisms, blood DNA methylation age and long-term ambient PM2.5 exposure in elderly men.

Author information

1
Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
2
Department of Environmental Health Sciences, Columbia Mailman School of Public Health, New York, NY, USA.
3
Department of Environmental Medicine & Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4
Center for Population Epigenetics, Department of Preventive Medicine, Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
5
VA Normative Aging Study, Veterans Affairs Boston Healthcare System & the Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
6
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Abstract

AIM:

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 (β = -1.13; 95% CI: -2.26 to -0.002). However, the association of PM2.5 with DNAm-age was significantly (Pinteraction  = 0.01) weaker in homozygous carriers of the major rs4961280 [AGO2] allele (β = 0.38; 95% CI: -0.20 to 0.96) when compared with all other participants (β = 1.58; 95% CI: 0.76 to 2.39). Our results suggest that miRNA processing impacts DNAm-age relationships. Graphical abstract: miRNA processing AGO2 polymorphism (rs4961280) modifies the association of long-term ambient fine particle exposure with blood DNA methylation age [Formula: see text] 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.

KEYWORDS:

AGO2; PM2.5; SNPs; air pollution; epigenetic aging; miRNA

PMID:
29106301
PMCID:
PMC5704092
[Available on 2018-12-01]
DOI:
10.2217/epi-2017-0094
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center