Gene–nutrient and gene–gene interactions of controlled folate intake by Japanese women

Elevated serum total homocysteine (tHcy) levels are associated with increased risk for cardiovascular disease and dementia. The prevalence rates of homozygous mutants among Japanese women ( n =300) were 17.3%, 1.3%, 18.6%, and 5.3% for methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, reduced folate carrier (RFC-1) A80G, and methionine synthase (MS) A2756G, respectively. The tHcy value was significantly lower ( p <0.001) in young women with CC or CT of MTHFR than with TT (10.9 ± 4.7 μmol/L) ( n =250). Diversities of serum folate and tHcy in women with 23 combinations of different alleles at low folate intake converged to the highest (34.0 ± 8.6 nmol/L) and lowest (7.6 ± 1.5 μmol/L) levels, respectively, after folic acid (400 μg/day) supplementation. In the regression equation ( y = ax + b ) of serum folate ( y nmol/L) plotted against mean folate intake ( x μg/day), the values of “ a ” were 0.032, 0.037, and 0.045 for individuals with CC, CT, and TT alleles, respectively, of MTHFR.