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 mumol/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 mumol/L) levels, respectively, after folic acid (400 mug/day) supplementation. In the regression equation (y = ax + b) of serum folate (y nmol/L) plotted against mean folate intake (x mug/day), the values of "a" were 0.032, 0.037, and 0.045 for individuals with CC, CT, and TT alleles, respectively, of MTHFR. (C) 2004 Elsevier Inc. All rights reserved.