Mutant Maternal and Fetal Thrombophilic Genotypes as a Risk Factor for Preeclampsia

L. M. Procopciuc, G. Caracostea, G. Zaharie, M. Puşcaş, G. Iordache, I. Olteanu, F. Stamatian

Abstract: The objectives are: 1. to determine the mutant thrombophilic genotypes (factor V Leiden mutation, 20210G®A mutation in the prothrombin gene, 677C®T and 1298A®C mutations in the metylenetetrahydropholate reductase gene) in the 26 pairs - preeclamptic mother/newborn of preeclamptic mother and 33 pairs - mother with normal pregnancy/newborn of mother with normal pregnancy 2. to calculate a risk score for different types of preeclampsia associated with the presence of genetic thrombophilias 3. to analyse the fetal thrombophilic genes in association with maternal genes as risk factors for preeclampsia. Mutant and normal genotypes for the four thrombophilic mutations were determined using the PCR-RFLP methods. The relative risk (odds ratio- OR) and confidence interval (95%CI) were calculated. p values lower than 0.05 were considered statistically significant. The Fisher exact test table 2x2 was used. The risk of preeclampsia was 4.36 (p= 0.2), 5.55 (p = 0.003) and 1.25 (p= 0.8) in association with factor V Leiden, 677C®T and 1298A®C, respectively mutation. None of the subjects included the study was identified as positive for the 20210G®A mutation in the prothrombin gene. The risk of preeclampsia was significantly increased in the case of presence of multiple thrombophilias (OR 4.4, p = 0.019). The 677C®T mutation represents higher risk factor for mild and severe preeclampsia (OR 12.5, p = 0.03 and OR 19.6, p = 0.005, respectively). Multiple thrombophilias presence confers a risk of 7 (p = 0.02) for the severe forms of preeclampsia. The frequency of 677C®T mutation and multiple thrombophilia in newborns of preeclamptic mothers was significantly more increased compared to the frequency in the group of newborns from normal pregnant mothers (73.07% vs. 39.39% and 38.46% vs. 12.12%, respectively). The risk of preeclampsia is significantly increased when the 677C®T mutant genotypes or multiple thrombophilias are present both in the mother and the child (OR 6.53, p = 0.002 and OR 4.65, p = 0.06, respectively). Our results emphasize the role of genetic thrombophilia in the development of different forms of preeclampsia. There is a mutant maternal/fetal genotype interaction, as a risk factor for preeclampsia. The presence of multiple thrombophilias in both the mother and the child is a risk factor for the development of preeclampsia.
Keywords: genetic thrombophilias, preeclampsia, PCR-RFLP methods