5,10-methylenetetrahydrofolate reductase common mutations, folate status and plasma homocysteine in healthy French adults of the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) cohort

The 677cytosine (c) --> thymine(T) mutation identified in the 5,10-methylen etetrahydrofolate reductase (MTHFR) gene has been frequently associated wit h an elevated plasma homocysteine concentration. The aim of the present stu dy was to determine the impact of this MTHFR common mutation on plasma and erythrocyte folate (RCF) and plasma total homocysteine (tHcy) concentration s in healthy French adults. A cohort of 291 subjects living in the Paris ar ea and participating in the Supplementation en Vitamines et Mineraux Antiox ydants (SU.VI.MAX) study were analysed to assess the impact of MTHFR polymo rphism 677C --> T on folate status and plasma tHcy concentration. The frequ ency of the mutant homozygote for 677C --> T polymorphism (677TT genotype) in the present cohort was 16.8%. There were significant differences in plas ma tHcy between 677CC, 677CT and 677TT genotype groups. The RCF concentrati ons were significantly different between each genotype, the lowest levels b eing associated with the 677TT genotype. When segregated by gender, no diff erences in tHcy between homozygous 677TT, heterozygous 677CT and wild-type 677CC genotype groups in women were observed. The fasting tHcy in women was unrelated to the 677C --> T mutation. However, tHcy was significantly incr eased in men with the homozygous 677TT genotype. We also analysed the possi ble implication of a second new MTHFR polymorphism (1298A --> C) in subject s with mild hyperhomocysteinaemia (4th quartile of homocysteinaemia; tHcy > 11.1 mu mol/l). The polymorphism 1298A --> C did not have a notable effect on tHcy or on the RCF levels. Our observations confirm a relatively high fr equency of the 677TT genotype in the French population. Women with this gen otype did not show the same increase in tHcy observed in men. Tn the presen t study dietary folate intake was not measured. Thus, the interaction of di etary folate with the MTHFR genotype in the French population needs further study.