Choline Intake, Plasma Riboflavin, and the Phosphatidylethanolamine N-Methyltransferase G5465A Genotype Predict Plasma Homocysteine in Folate-Deplete Mexican-American Men with the Methylenetetrahydrofolate Reductase 677TT Genotype

• Published in: The Journal of nutrition Vol. 139; no. 4; pp. 727 - 733
• Main Authors: Caudill, Marie A, Dellschaft, Neele, Solis, Claudia, Hinkis, Sabrina, Ivanov, Alexandre A, Nash-Barboza, Susan, Randall, Katharine E, Jackson, Brandi, Solomita, Gina N, Vermeylen, Francoise
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Nutrition 01.04.2009
• Subjects: Adolescent; Adult; Biological and medical sciences; blood chemistry; blood plasma; choline; common mutation; disease; Feeding. Feeding behavior; folic acid; Folic Acid - pharmacology; Fundamental and applied biological sciences. Psychology; Genotype; homocysteine; Homocysteine - blood; Humans; liquid-chromatography; Male; mass-spectrometry; men; metabolism; methyl balance; methylenetetrahydrofolate reductase; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; Methylenetetrahydrofolate Reductase (NADPH2) - metabolism; methylenetetrahydrofolate reductase 677TT genotype; methyltransferases; Mexican Americans; Mexican Americans - ethnology; Mexican Americans - genetics; Middle Aged; Mutation - genetics; nutrient intake; nutrition assessment; nutritional status; Phosphatidylethanolamine N-Methyltransferase - genetics; Phosphatidylethanolamine N-Methyltransferase - metabolism; phosphatidylethanolamine N-methyltransferase G5465A genotype; phosphatidylethanolamines; polymorphism; prediction; riboflavin; Riboflavin - blood; serum; Vertebrates: anatomy and physiology, studies on body, several organs or systems; young-women; United States; Human; Biological fluid; Phosphatidylethanolamine; Nutrition; Riboflavin; Genotype; B-Vitamins; Folic acid; Folate; Blood plasma; Micronutrient; Homocystein; Choline
• ISSN: 0022-3166; 1541-6100
• DOI: 10.3945/jn.108.100222

We previously showed that provision of the folate recommended dietary allowance and either 300, 550, 1100, or 2200 mg/d choline for 12 wk resulted in diminished folate status and a tripling of plasma total homocysteine (tHcy) in men with the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype. However, the substantial variation in tHcy within the 677TT genotype at wk 12 implied that several factors were interacting with this genotype to affect homocysteine. As an extension of this work, the present study sought to identify the main predictors of wk-12 plasma tHcy, alone and together with the MTHFR C677T genotype (29 TT, 31 CC), using linear regression analysis. A basic model explaining 82.5% of the variation (i.e. adjusted R² = 0.825) was constructed. However, the effects of the variables within this model were dependent upon the MTHFR C677T genotype (P for interaction [less-than or equal to] 0.021). Within the 677TT genotype, serum folate (P = 0.005) and plasma riboflavin (P = 0.002) were strong negative predictors (inversely related) explaining 12 and 15%, respectively, of the variation in tHcy, whereas choline intake (P = 0.003) and serum creatinine (P < 0.001) were strong positive predictors, explaining 19 and 25% of the variation. None of these variables, except creatinine (P = 0.021), correlated with tHcy within the 677CC genotype. Of the 8 additional polymorphisms tested, none appeared to influence tHcy. However, when creatinine was not in the model, the phosphatidylethanolamine N-methyltransferase 5465G[rightward arrow]A variant predicted lower tHcy (P < 0.001); an effect confined to the MTHFR 677TT genotype. Thus, in folate-deplete men, several factors with roles in 1-carbon metabolism interact with the MTHFR C677T genotype to affect plasma tHcy.