MTHFR methylation moderates the impact of smoking on DNA methylation at AHRR for African American young adults.
Am J Med Genet B Neuropsychiatr Genet
; 174(6): 608-618, 2017 Sep.
Article
em En
| MEDLINE
| ID: mdl-28436623
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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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Negro ou Afro-Americano
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Fumar
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Metilação de DNA
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Metilenotetra-Hidrofolato Redutase (NADPH2)
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
Limite:
Adolescent
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Adult
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Humans
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Male
Idioma:
En
Revista:
Am J Med Genet B Neuropsychiatr Genet
Assunto da revista:
GENETICA MEDICA
/
NEUROLOGIA
/
PSIQUIATRIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Geórgia