MTHFR C677T Polymorphism is Associated with Low Levels of Folic Acid in the InChianti Study

Abstract number: P0479

Gori AM, Corsi AM, Alessandrello, Liotta A, Falciani M, Mannini L, Brogi D, Bandinelli B, Fedi S, Fatini C, Ferrucci L, Abbate R, Gensini GF

Impaired folate status is associated with increased risk of several conditions such as cardiovascular disease and stroke. Methylenetetrahydrofolate reductase (MTHFR) is a regulating enzyme in folate-dependent homocysteine remethylation. The aim of this study was to determine the relationship between homocysteine, vitamin B status and MTHFR genotypes in a population-based study which sampled people living in two sites in the surrounding of Florence (Italy), the InChianti Study. In the InChianti population the dietary intakes of folic acid, vitamin B6 and vitamin B12 did not significantly differ among MTHFR genotypes. General linear model analyses, after adjustment for age, sex, vitamin B6, B12 and folic acid intakes and creatinine levels demonstrated that homocysteine plasma levels were significantly (P < 0.01) higher in subjects TT homozygous (16.2, 95% CI 15.6–16.8 µMol/l) than in subjects with CT (13.6, 95% CI 13.3–14.0 µMol/l) and CC (13.5, 95% CI 13.0–13.9 µMol/l) genotypes. We also demonstrated that serum folate levels were related to MTHFR C677 genotype: folate levels were significantly (P < 0.01) lower in subjects carrying TT genotype (2.9 ng/ml 95% CI 2.7–3.2 ng/ml) than those observed in subjects with CC (3.5 ng/ml 95% CI 3.3–3.7 ng/ml) or CT (3.3 ng/ml 95% CI 3.2–3.5 ng/ml) genotypes of MTHFR C677T polymorphism. In particular, subjects with folic acid intake in the lowest tertile (<221.2 µg/die) and carrying MTHFR TT genotype had folate levels significantly (P < 0.01) lower (2.4 95% CI 1.9–2.8 ng/ml) than those found in subjects with CT (3.3 95% CI 3.0–3.6 ng/ml) and CC genotypes (3.4 95% CI 2.8–3.9 ng/ml), whereas only a trend was observed for subjects in the highest tertiles of folic acid intake. Our results showed that in the elderly population of the InChianti Study, the MTHFR TT genotype is related to low serum folic acid levels, especially in subjects with a low folic acid intake.