MTHFR Methylation Moderates the Impact of Smoking on DNA Methylation at AHRR for African American Young Adults

Overview

Journal Am J Med Genet B Neuropsychiatr Genet

Specialties Genetics
Neurology
Psychiatry

Date 2017 Apr 25

PMID 28436623

Citations 13

Authors

Steven R H Beach

Man Kit Lei

Mei Ling Ong

Gene H Brody

Meeshanthini V Dogan

Robert A Philibert

Affiliations

Soon will be listed here.

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.

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References

Shenker N, Polidoro S, van Veldhoven K, Sacerdote C, Ricceri F, Birrell M . Epigenome-wide association study in the European Prospective Investigation into Cancer and Nutrition (EPIC-Turin) identifies novel genetic loci associated with smoking. Hum Mol Genet. 2012; 22(5):843-51. DOI: 10.1093/hmg/dds488. View

Brody G, Yu T, Chen Y, Kogan S, Smith K . The Adults in the Making program: long-term protective stabilizing effects on alcohol use and substance use problems for rural African American emerging adults. J Consult Clin Psychol. 2011; 80(1):17-28. PMC: 3265673. DOI: 10.1037/a0026592. View

Okumura K, Tsukamoto H . Folate in smokers. Clin Chim Acta. 2011; 412(7-8):521-6. DOI: 10.1016/j.cca.2011.01.003. View

. Racial disparities in smoking-attributable mortality and years of potential life lost --- Missouri, 2003-2007. MMWR Morb Mortal Wkly Rep. 2010; 59(46):1518-22. View

Yi P, Melnyk S, Pogribna M, Pogribny I, Hine R, James S . Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem. 2000; 275(38):29318-23. DOI: 10.1074/jbc.M002725200. View

Piyathilake C, Hine R, Dasanayake A, Richards E, Freeberg L, Vaughn W . Effect of smoking on folate levels in buccal mucosal cells. Int J Cancer. 1992; 52(4):566-9. DOI: 10.1002/ijc.2910520412. View

Dogan M, Xiang J, Beach S, Cutrona C, Gibbons F, Simons R . Ethnicity and Smoking-Associated DNA Methylation Changes at HIV Co-Receptor GPR15. Front Psychiatry. 2015; 6:132. PMC: 4585036. DOI: 10.3389/fpsyt.2015.00132. View

Lewis S, Zammit S, Gunnell D, Davey Smith G . A meta-analysis of the MTHFR C677T polymorphism and schizophrenia risk. Am J Med Genet B Neuropsychiatr Genet. 2005; 135B(1):2-4. DOI: 10.1002/ajmg.b.30170. View

Stern L, Mason J, Selhub J, Choi S . Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene. Cancer Epidemiol Biomarkers Prev. 2000; 9(8):849-53. View

10.

Dolzhenko E, Smith A . Using beta-binomial regression for high-precision differential methylation analysis in multifactor whole-genome bisulfite sequencing experiments. BMC Bioinformatics. 2014; 15:215. PMC: 4230021. DOI: 10.1186/1471-2105-15-215. View

11.

Walmsley C, Bates C, Prentice A, Cole T . Relationship between cigarette smoking and nutrient intakes and blood status indices of older people living in the UK: further analysis of data from the National Diet and Nutrition Survey of people aged 65 years and over, 1994/95. Public Health Nutr. 1999; 2(2):199-208. DOI: 10.1017/s1368980099000257. View

12.

Zeilinger S, Kuhnel B, Klopp N, Baurecht H, Kleinschmidt A, Gieger C . Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS One. 2013; 8(5):e63812. PMC: 3656907. DOI: 10.1371/journal.pone.0063812. View

13.

Peerbooms O, van Os J, Drukker M, Kenis G, Hoogveld L, De Hert M . Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: evidence for a common genetic vulnerability?. Brain Behav Immun. 2010; 25(8):1530-43. DOI: 10.1016/j.bbi.2010.12.006. View

14.

Sherry S, Ward M, Kholodov M, Baker J, Phan L, Smigielski E . dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 2000; 29(1):308-11. PMC: 29783. DOI: 10.1093/nar/29.1.308. View

15.

Philibert R, Beach S, Lei M, Brody G . Changes in DNA methylation at the aryl hydrocarbon receptor repressor may be a new biomarker for smoking. Clin Epigenetics. 2013; 5(1):19. PMC: 3819644. DOI: 10.1186/1868-7083-5-19. View

16.

Elliott H, Tillin T, McArdle W, Ho K, Duggirala A, Frayling T . Differences in smoking associated DNA methylation patterns in South Asians and Europeans. Clin Epigenetics. 2014; 6(1):4. PMC: 3915234. DOI: 10.1186/1868-7083-6-4. View

17.

Beach S, Gerrard M, Gibbons F, Brody G, Philibert R . A Role for Epigenetics in Broadening the Scope of Pediatric Care in the Prevention of Adolescent Smoking. Epigenet Diagn Ther. 2016; 1(2):91-97. PMC: 4972497. DOI: 10.2174/2214083201999140320153918. View

18.

Mokdad A, Marks J, Stroup D, Gerberding J . Actual causes of death in the United States, 2000. JAMA. 2004; 291(10):1238-45. DOI: 10.1001/jama.291.10.1238. View

19.

Goyette P, Rozen R . The thermolabile variant 677C-->T can further reduce activity when expressed in cis with severe mutations for human methylenetetrahydrofolate reductase. Hum Mutat. 2000; 16(2):132-8. DOI: 10.1002/1098-1004(200008)16:2<132::AID-HUMU5>3.0.CO;2-T. View

20.

Stover P . One-carbon metabolism-genome interactions in folate-associated pathologies. J Nutr. 2009; 139(12):2402-5. PMC: 2777484. DOI: 10.3945/jn.109.113670. View