Patterns of co-occurrence of three single nucleotide polymorphisms of the 5,10-methylenetetrahydrofolate reductase gene in kidney transplant recipients

Background Recently, a new mutation of the 5,10-methylenetetrahydrofolate reductase (MTHFR) encoding gene was first described (1793G > A). Only few reports have studied the prevalence of this polymorphism, especially in combination with other MTHFR mutations (677C > T, 1298A > C). Methods We cross-sectionally identified the novel MTHFR 1793G > A polymorphism in 730 kidney transplant recipients. MTHFR 677C > T and 1298A > C were also assessed and the frequency of each was described individually as well as in cross-tabulation with the other MTHFR genotypes. The expected number of patients for each MTHFR genotype combination was calculated and contrasted with the observed numbers. Fisher's exact test was used for statistical inference. Results The allelic frequency of MTHFR 1793G > A was 0.052. Seventy-two patients (9.9%) were heterozygous and two patients (0.3%) were homozygous. From the cross-tabulations, we identified 53 patients (expected: 33.6) with the MTHFR 1298AC/1793GA genotype and 17 patients (expected: 6.7) with the MTHFR 1298CC/1793GA genotype. Furthermore, we found two patients with double homozygosity for MTHFR 1793G > A and MTHFR 1298A > C (MTHFR 1793AA/1298CC genotype). The frequencies of these genotype combinations were substantially larger than could be expected (P < 0.001). Conclusions These findings suggest a selection or survival advantage for individuals with combined MTHFR 1793G > A and MTHFR 1298A > C genotypes, possibly owing to a mutually stabilizing effect on MTHFR enzyme activity.