Increased prevalence of combined MTR and MTHFR genotypes among individuals with severely elevated total homocysteine plasma levels

The prevalence of the methionine synthase (MTR) 2756A -->G polymorphism among individuals with severely elevated total homocysteine (tHcy) plasma levels is unknown. Therefore, 1,716 subjects, including 415 hemodialysis patients, 179 peritoneal dialysis patients, 733 kidney graft recipients, and 389 healthy subjects, were investigated. The distribution of MTR 2756A -->G, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C -->T/1298A -->C, genotypes among study participants with extremely high tHcy plasma levels (>90th percentile) was compared with the genotype distribution of subjects with very low tHcy plasma levels (<10th percentile). The prevalence of MTR 2756AG and GG genotypes alone did not differ between individuals with extremely high or extremely low tHcy levels (P = 0.7402; odds ratio [OR], 1.076; 95% confidence interval [CI], 0.697 to 1.662). Conversely, combined MTR and MTHFR genotypes, (MTR 2756AG and 2756GG and MTHFR 677TT/1298AA and 677CT/1298AC) were found more often in the highest (n = 34) compared with the lowest plasma tHcy decile (n = 19; P = 0.0252; OR, 1.983; 95% Cl, 1.079 to 3.643). The number of patients with the wild-type MTR and MTHFR genotype was three times greater in the lowest compared with the highest decile (17 versus 6 patients, respectively; P = 0.0155; OR, 0.330; 95% Cl, 0.126 to 0.861). In summary, our study shows that the 2756A<right arrow>G transition of MTR in combination with MTHFR 677TT/1298AA and 677CT/1298AC can be associated with extremely high tHcy plasma levels. (C) 2001 by the National Kidney Foundation, Inc.