Prevalence of methylenetetrahydrofolate reductase mutations in patients with venous thrombosis

Background: The objectives of this study are to examine the prevalence of combined methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298A-->C mutations in patients with venous thrombosis (VT) and healthy volunteers and to determine if these mutations are in Hardy-Weinberg equilibrium. Methods and Results: Sixty-five patients with VT and 64 healthy volunteers were assessed for MTHFR 677T and 1298C alleles using polymerase chain reaction and restriction fragment length polymorphism. Observed MTHFR genotype frequencies were compared with expected genotype combinations, and their odds ratios were determined. MTHFR allele frequency did not differ between VT and control groups; however, differences were observed for MTHFR genotype distribution. MTHFR 677T and 1298C alleles occurred in cis in our population, and therefore mutation crossover has occurred. There was deviation from the Hardy-Weinberg equilibrium for combined MTHFR genotypes, although this may at least partly be attributable to linkage disequilibrium. MTHFR 677CT/1298CC and 677TT/1298CC genotypes (P < .05) were not observed in either group. Conclusions: The absence of MTHFR 677CT/1298CC and 677TT/1298CC genotypes in both groups suggests that certain MTHFR genotypes may carry a selective advantage. Our discovery of a substantial number of MTHFR mutations in cis configuration suggests that any MTHFR allele linkage disequilibrium present is incomplete.