title: Association of dietary and genetic factors related to one-carbon metabolism with global methylation level of leukocyte DNA.
abstract: Global hypomethylation of leukocyte DNA has been associated with an increased risk of cancer. As dietary and genetic factors related to one-carbon metabolism may influence both the methylation and synthesis of DNA, we investigated associations between these factors and the global methylation level of peripheral blood leukocyte DNA based on a cross-sectional study of 384 Japanese women. Dietary intake of folate and vitamins B2, B6, and B12 was assessed with a validated semiquantitative food frequency questionnaire. Five polymorphisms in methylenetetrahydrofolate reductase (MTHFR) (rs1801133 and rs1801131), methionine synthase (MTR) (rs1805087), and methionine synthase reductase (MTRR) (rs10380 and rs162049) were genotyped. Global DNA methylation of leukocyte DNA was quantified using Luminometric Methylation Assay. A linear trend of association between methylation and dietary and genetic factors was evaluated by regression coefficients in a multivariable linear regression model. Mean global methylation level (standard deviation) was 70.2% (3.4) and range was from 59.0% to 81.2%. Global methylation level significantly decreased by 0.36% (95% confidence interval, 0.03-0.69) per quartile category for folate level. Subgroup analysis suggested that alcohol drinking modified the association between folate intake and global methylation level (P(interaction)  = 0.01). However, no statistically significant association was observed for intake of vitamins B2, B6, and B12, alcohol consumption, or five single nucleotide polymorphisms of MTHFR, MTR, and MTRR. We found that higher folate intake was significantly associated with a lower level of global methylation of leukocyte DNA in a group of healthy Japanese females.
authors.affiliation: Division of Genetics, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Hiroe
authors.initials: H
authors.lastname: Ono
authors.forename: Motoki
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Aya
authors.initials: A
authors.lastname: Kuchiba
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kasuga
authors.forename: Shiro
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Onuma
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishimura
authors.forename: Ritsu
authors.initials: R
authors.lastname: Kusama
authors.forename: Sumiko
authors.initials: S
authors.lastname: Ohnami
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsugane
mesh_terms: D000328:Adult; D000368:Aged; D002244:Carbon / Q000378:metabolism*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D004032:Diet; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D014805:Vitamin B 12 / Q000008:administration & dosage; D025101:Vitamin B 6 / Q000008:administration & dosage; D014815:Vitamins / Q000008:administration & dosage
chemical_list: D014815:Vitamins; D002244:Carbon; D025101:Vitamin B 6; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12