Are the associations between life-style related factors and plasma total homocysteine concentration different according to polymorphism of 5,10-methylenetetrahydrofolate reductase gene (C677T MTHFR)? A cross-sectional study in a Japanese rural population.

Mild hyperhomocysteinemia is one of the known strong risk factors for atherosclerotic diseases, and therefore it is important to clarify factors that could determine plasma total homocysteine (tHcy) level. A cross-sectional study with a random sample of 455 Japanese rural residents aged 40-69 years was conducted in 2000 to investigate the associations of plasma tHcy concentration with 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and selected life-style related factors. The frequency of the mutant allele, Valine (V) allele, was 0.40 and the prevalence of VV genotype was 14.3%. Plasma tHcy concentration in VV was significantly higher than those in two other genotypes. There were significant inverse associations of plasma tHcy with serum folate and serum vitamin B12 (P<0.001 for trend, respectively); both being stronger in VV than in other genotypes. The number of cigarettes smoked per day was positively associated with plasma tHcy concentration. A multivariate regression analysis revealed that serum folate, serum vitamin B12, and MTHFR genotype were independently associated with plasma tHcy. The inter-individual variance of plasma tHcy was more explained by serum folate and vitamin B12 than by MTHFR genotype. Higher intakes of folate, vitamin B12, and non-smoking may be important to prevent mild hyperhomocysteinemia and the eventual atherosclerotic diseases in this Japanese rural population.