Mutations in the gene for methylenetetrahydrofolate reductase, homocysteine levels, and vitamin status in women with a history of preeclampsia

OBJECTIVE: This study was undertaken to assess frequencies of the methylene tetrahydrofolate reductase gene mutations cytosine-to-thymine substitution at base 677 (C677T) and adenine-to-cytosine substitution at base 1298 (A129 8C) and their interactions with homocysteine and vitamin levels among Dutch women with preeclampsia. STUDY DESIGN: Mutations were studied in the following 5 groups: 47 consecut ive women with preeclampsia, 49 women with preeclampsia and with hyperhomoc ysteinemia, 36 women with preeclampsia but without hyperhomocysteinemia, 12 7 women with familial preeclampsia (typed for C677T mutations only), and 12 0 control subjects. Plasma levels of homocysteine, folate, and vitamin B-12 were measured. RESULTS: Although 10.6% of the consecutive women with preeclampsia had stri ctly defined hyperhomocysteinemia (values >97.5th percentile), neither muta tion was found in excess relative to the control group. Women with preeclam psia who had mild hyperhomocysteinemia (values >75th percentile) had a sign ificant excess of the TT genotype (homozygosity for C677T mutation) relativ e to the women with preeclampsia who did not have hyperhomocysteinemia (odd s ratio, 8.2: 95% confidence interval. 1.8-39). They also had significantly lower vitamin levels. CONCLUSION: Hyperhomocysteinemia in women with preeclampsia was associated with mutations in the gene for methylenetetrahydrofolate reductase, but the high frequency of hyperhomocysteinemia itself cannot be explained by these mutations alone.