Riboflavin as a determinant of plasma total homocysteine: Effect modification by the methylenetetrahydrofolate reductase C677T polymorphism

Background: Plasma total homocysteine (tHcy) is a risk factor for cardiovas cular disease. tHcy concentrations are partly determined by folate, cobalam in, and vitamin B-6 status, and methyfenetetrahydrofolate reductase (MTHFR) and other flavoenzymes are important for the biotransformation of these vi tamins. This motivates the investigation of the possible relationship betwe en riboflavin status and tHcy. Methods: The study had a cross-sectional design and included 423 healthy bl ood donors, ages 19-69 years. We determined plasma tHcy, serum folate, seru m cobalamin, serum creatinine, and MTHFR C677T genotype. In addition, we me asured riboflavin and its two coenzyme forms, flavin mononucleotide and fla vin adenine dinucleotide, in EDTA plasma by capillary electrophoresis and l aser-induced fluorescence detection. Results: Riboflavin determined tHcy independently in a multiple linear regr ession model with adjustment for sex, age, folate, cobalamin, creatinine, a nd MTHFR genotype (P = 0.008). tHcy was 1.4 mu mol/L higher in the lowest c ompared with the highest riboflavin quartile. The riboflavin-tHcy relations hip was modified by genotype (P = 0.004) and was essentially confined to su bjects with the C677T transition of the MTHFR gene. Conclusions: Plasma riboflavin is an independent determinant of plasma tHcy . Studies on deficient populations are needed to evaluate the utility of ri boflavin supplementation in hyperhomocysteinemia. (C) 2000 American Associa tion for Clinical Chemistry.