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

Abstract

The effect of the combined 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T and 1298A→C genotype on total homocysteine (tHcy), folate, and vitamin B12 plasma levels was investigated in 983 subjects, including 415 hemodialysis patients, 179 peritoneal dialysis patients, and 389 healthy individuals. Mean tHcy plasma concentrations were 27.2 ± 15.8 μmol/L in hemodialysis patients, 25.4 ± 19.1 μmol/L in peritoneal dialysis patients, and 8.9 ± 3.5 μmol/L in healthy individuals. Hyperhomocysteinemia (tHcy > 15 μmol/L) was detected in 81.6% of patients and 2.6% of controls. 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 B12 plasma level were significant predictors of tHcy plasma levels. Analysis of variance showed that this effect of MTHFR genotypes on tHcy level was caused by significantly greater tHcy levels in 677TT/1298AA hemodialysis and peritoneal dialysis patients versus other genotypes. Compound heterozygous controls (677CT/1298AC genotype) had significantly greater tHcy levels compared with 677CC/1298AA controls. There was no major effect of MTHFR polymorphisms on folate and vitamin B12 plasma concentrations. This study shows that the MTHFR 677TT/1298AA genotype, but not the 677CT/1298AC genotype, is a significant predictor of tHcy plasma levels in dialysis patients. © 2001 by the National Kidney Foundation, Inc.