Riboflavin status modifies the effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms on homocysteine

Abstract

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase red uctase (MTRR), riboflavin- dependent enzymes, participat e in homocysteine metabolism. Reported effects of riboflavin status on the association between the MTHFR 677C [ T polymorphism and homocysteine vary, and the effects of the MTRR 66A [ Gor MTRR 524C [ Tpoly- morphisms on homocysteine are unclear. We tested the hypothesis that the effects of the MTHFR 677C [ T, MTRR 66A [ Gand MTRR 524C [ T polymorphisms on fasting plasma total homocysteine (tHcy) depen d on riboflavin status (eryth- rocyte glutathionine reductase activation coefficient, optimum: \ 1.2; marginally deficient: 1.2–1.4; deficient: C 1.4) in 771 adults aged 18–75 years. MTHFR 677T allele carriers with middle or low tertile plasma folate ( \ 14.7 nmol/L) had 8.2 % higher tHcy compared to the 677CC genotype ( p \ 0.01). This effect was eliminated when riboflavin status was optimal ( p for interaction: 0.048). In the lowest cobalamin quartile ( B 273 pmol/L), riboflavin status modifies the relationship between the MTRR 66 A [ G polymorphism and tHcy ( p for interaction: 0.034). tHcy was 6.6 % higher in MTRR 66G allele carriers compared to the 66AA genotype with marginally deficient or optimal riboflavin status, but there was no differ- ence when riboflavin status was deficient ( p for interaction: 0.059). tHcy was 13.7 % higher in MTRR 524T allele carriers compared to the 524CC genoty pe when cobalamin status was low ( p \ 0.01), but no difference was observed when we stratified by riboflavin status. The effect of the MTHFR 677C [ T polymorphism on tHcy depends on riboflavin status, that of the MTRR 66A [ G polymorphism on cobalamin and riboflavin status and that of the MTRR 524C [ T polymorphism on cobalamin status