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Am J Med Genet B Neuropsychiatr Genet. 2017 Sep;174(6):608-618. doi: 10.1002/ajmg.b.32544. Epub 2017 Apr 24.

MTHFR methylation moderates the impact of smoking on DNA methylation at AHRR for African American young adults.

Author information

1
Department of Psychology, University of Georgia, Athens, Georgia.
2
University of Georgia, Center for Family Research, Athens, Georgia.
3
College of Engineering, University of Iowa, Iowa City, Iowa.
4
Department of Psychiatry, University of Iowa, Iowa City, Iowa.

Abstract

Smoking has been shown to have a large, reliable, and rapid effect on demethylation of AHRR, particularly at cg05575921, suggesting that methylation may be used as an index of cigarette consumption. Because the availability of methyl donors may also influence the degree of demethylation in response to smoking, factors that affect the activity of methylene tetrahydrofolate reductase (MTHFR), a key regulator of methyl group availability, may be of interest. In the current investigation, we examined the extent to which individual differences in methylation of MTHFR moderated the association between smoking and demethylation at cg05575921 as well as at other loci on AHRR associated with a main effect of smoking. Using a discovery sample (AIM, N = 293), and a confirmatory sample (SHAPE, N = 368) of young adult African Americans, degree of methylation of loci in the first exon of MTHFR was associated with amplification of the association between smoking and AHRR demethylation at cg05575921. However, genetic variation at a commonly studied MTHFR variant, C677T, did not influence cg05575921 methylation. The significant interaction between MTHFR methylation and the smoking-induced response at cg05575921 suggests a role for individual differences in methyl cycle regulation in understanding the effects of cigarette consumption on genome wide DNA methylation.

KEYWORDS:

AHRR; African American; MTHFR; folate; methylation; smoking

PMID:
28436623
PMCID:
PMC5561486
DOI:
10.1002/ajmg.b.32544
[Indexed for MEDLINE]
Free PMC Article

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