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Methylation of MTHFR Moderates the Effect of Smoking on Genomewide Methylation Among Middle Age African Americans
Journal article   Open access   Peer reviewed

Methylation of MTHFR Moderates the Effect of Smoking on Genomewide Methylation Among Middle Age African Americans

Allan M Andersen, Man-Kit Lei, Robert A Philibert and Steven R. H Beach
Frontiers in genetics, Vol.9, pp.622-622
12/10/2018
DOI: 10.3389/fgene.2018.00622
PMID: 30619455
url
https://doi.org/10.3389/fgene.2018.00622View
Published (Version of record) Open Access

Abstract

Differential methylation at MTHFR (m MTHFR) has been examined previously as a moderator of changes in methylation among nascent smokers, but the effects of mMTHFR on genomewide patterns of methylation among established smokers in middle age are unknown. In the current investigation we examined a sample of 180 African American middle-aged smokers and non-smokers to test for patterns indicative of three different potential mechanisms of impact on epigenetic remodeling in response to long-term smoking. We found that m MTHFR moderated the association between smoking and changes in methylation for more than 25% of the 909 loci previously identified as being associated with smoking at a genomewide level of significance in middle-aged African Americans. Observed patterns of effect indicated amplification of both hyper and hypo methylating responses to smoking among those with lower m MTHFR . Moderating effects were robust to controls for sex, age, diet, and cell-type variation. Implications for potential mechanisms conferring effects are discussed. Of particular potential practical importance was a strong effect of m MTHFR on hypomethylation at GPR15 in response to smoking, indicative of the differential impact of MTHFR activity on changes in a specific cell population linked to inflammatory disease in smokers.
GPR15 digital PCR smoking DNA methylation Genetics AHRR cg19859270 cg05575921 epigenetics

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