Associations between MTHFR 1793G>A and plasma total homocysteine, folate, and vitamin B in kidney transplant recipients.

Abstract

Currently, no evidence is available on the putative associations between a novel single nucleotide polymorphism of the 5,10-methylenetetrahydrofolate reductase gene MTHFR 1793G>A and plasma levels of vitamin B(12), folate, or total homocysteine (tHcy). In a cross-sectional study of 730 kidney allograft recipients, patients were categorized by MTHFR 1793G>A genotype. In univariate and multivariate linear regression models that allowed the outcome variables vitamin B(12), folate, and tHcy plasma levels to follow a gamma distribution, we tested for possible associations of allelic variants of MTHFR 1793G>A and these three dependent variables. As hypothesized in previous work, we specifically evaluated possible effect modification between the MTHFR 1793G>A and 1298A>C mutations on these outcomes. The allele frequency for MTHFR 1793G>A was 0.052. Heterozygosity (N= 72) or homozygosity (N= 2) for MTHFR 1793G>A was not independently associated with plasma levels of vitamin B(12) (P= 0.33) or tHcy (P= 0.70), but a borderline association with higher folate concentrations was detected (Deltafolate = 1.91 nmol/L) (95% CI -0.03 to 3.86 nmol/L) (P= 0.05). Further, we found strong and significant positive interactions between the MTHFR 1793G>A and 1298A>C mutations on vitamin B(12) concentrations. Higher folate concentrations in kidney transplant recipients with MTHFR 1793GA or 1793AA and markedly higher concentrations of vitamin B(12) in patients with combined MTHFR 1793G>A and 1298A>C mutations may contribute to the survival advantage that has been postulated for such patients showing these genotypes.