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MTHFR methylation moderates the impact of smoking on DNA methylation at AHRR for African American young adults
Journal article   Peer reviewed

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

Steven R H Beach, Man Kit Lei, Mei Ling Ong, Gene H Brody, Meeshanthini V Dogan and Robert A Philibert
American journal of medical genetics. Part B, Neuropsychiatric genetics, Vol.174(6), pp.608-618
09/2017
DOI: 10.1002/ajmg.b.32544
PMCID: PMC5561486
PMID: 28436623
url
https://www.ncbi.nlm.nih.gov/pmc/articles/5561486View
Open Access

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.
Young Adult DNA Methylation Basic Helix-Loop-Helix Transcription Factors - genetics Methylenetetrahydrofolate Reductase (NADPH2) - genetics Epigenesis, Genetic Humans Adolescent African Americans - genetics Repressor Proteins - genetics Adult Male Smoking - genetics

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