Association of two MTHFR polymorphisms with total homocysteine plasma levels in dialysis patients

The effect of the combined 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C -->T and 1298A -->C genotype on total homocysteine (tHcy), folate, an d vitamin B-12 plasma levels was investigated in 983 subjects, including 41 5 hemodialysis patients, 179 peritoneal dialysis patients, and 389 healthy individuals. Mean tHcy plasma concentrations were 27.2 +/- 15.8 mu mol/L in hemodlalysis patients, 25.4 +/- 19.1 mu mol/L in peritoneal dialysis patie nts, and 8.9 +/- 3.5 mu mol/L in healthy individuals. Hypyperhomocysteinemi a (tHcy > 15 mu mol/L) was detected in 81.6% of patients and 2.6% of contro ls, Multiple stepwise regression analysis showed that the MTHFR 677C --> T/ 1298A -->C genotype (CC/AA, CC/AC, CC/CC, CT/AA, CT/AC, TT/AA), vitamin use , age, folate and vitamin B-12 plasma level were significant predictors of tHcy plasma levels. Analysis of variance showed that this effect of MTHFR g enotypes on tHcy level was caused by significantly greater tHcy levels in 6 77TT/1298AA hemodialysis and peritoneal dialysis patients versus other geno types, Compound heterozygous controls (677CT/1298AC genotype) had significa ntly greater tHcy levels compared with 677CC/1298AA controls. There was no major effect of MTHFR polymorphisms on folate and vitamin B-12 plasma conce ntrations. This study shows that the MTHFR 677TT/1298AA genotype, but not t he 677CT/1298AC genotype, is a significant predictor of tHcy plasma levels in dialysis patients. (C) 2001 by the National Kidney Foundation, Inc.