Methylenetetrahydrofolate reductase polymorphisms in preeclampsia and the HELLP syndrome

Objective: To investigate the prevalence of the 677 (C → T) and 1298 (A → C) polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene in our preeclamptic population. For a summary estimation of the risk of the 677 (C → T) polymorphism for preeclampsia, we also performed a meta-analysis on four previously published case-control studies to which our results were added. Methods: Genotypes were analyzed by polymerase chain reaction followed by restriction enzyme analysis. The results of 176 nonpregnant women, previously hospitalized for preeclampsia in a tertiary care center, were compared with 403 Dutch population-based controls. Results were statistically analyzed with a chi-square test. Mean Outcome Measures: The incidence of the 677 (C → T) and 1298 (A → C) polymorphisms in the MTHFR gene. Results: The incidence of both MTHFR missense polymorphisms was not significantly different between cases and controls. We found an odds ratio (OR) of 1.5 [95% confidence interval (CI) 0.8-2.6, p = 0.17] and an OR of 1.0 (95% CI 0.6-1.9, p = 0.23) for the 677 (C → T) and the 1298 (A → C) polymorphism, respectively, in cases comparing the prevalence of the homozygous genotype versus the other two genotypes. The meta-analysis resulted in a significant OR of 2.0 (95% CI 1.4-2.9). Conclusions: In contrast to four previous studies, we were neither able to confirm an increased risk for preeclampsia to the 677 (C → T) polymorphism nor did we find an increased risk for preeclampsia to the 1298 (A → C) polymorphism. From the meta-analysis, however, we conclude that it cannot be ruled out that the homozygous 677TT genotype is a modest but significant risk factor for preeclampsia.

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