Methylenetetrahydrofolate reductase polymorphism, folate, and susceptibility to preeclampsia

OBJECTIVES: To test the hypothesis that the common missense mutation of 5, 10-methylenetetrahydro-folate reductase (MTHFR) (677 C to T, ala to val) is more prevalent among nulliparous preeclamptic women compared with control and transient hypertension of pregnancy patients. The correlation of the MT HFR T677/T677 genotype in mothers and fetuses was also investigated to test for possible maternal-fetal interactions. Lastly, possible differences in serum folate concentrations between control and preeclampsia patients and t he possibility of a correlation between serum folate and MTHFR genotype wer e investigated as well. METHODS: The MTHFR genotype was determined for 114 control subjects, 99 pre eclamptic patients, and 24 patients with transient hypertension of pregnanc y by a polymerase chain reaction/restriction fragment length polymorphism ( PCR) method. To ensure homogeneity of ethnic background, only samples from white women were analyzed. Results were analyzed with a chi(2) test for hom ogeneity. Serum folate was determined by radioimmunoassay (RIA). RESULTS: the prevalence of the MTHFR T677/T677 genotype was not significant ly different between the populations studied. There was no significant diff erence in the prevalence of the MTHFR T677/T677 genotype between the infant s of preeclamptic and control mothers. Furthermore, there was no difference in serum folate concentrations between control and preeclampsia patients, and there was no correlation between serum folate and MTHFR genotype. CONCLUSION: These data suggest that contrary to previous published reports, the C677T missense mutation of MTHFR is not a risk factor for preeclampsia in this nulliparous patient population. Furthermore, this mutation is not related to serum folate status in late pregnancy. Copyright (C) 1999 by the Society for Gynecologic Investigation.