Mutations in the thrombomodulin and endothelial protein C receptor genes in women with late fetal loss

Late fetal loss can be associated with placental insufficiency and coagulat ion defects. Thrombomodulin (TM) and the endothelial protein C receptor (EP CR) are glycoprotein receptors expressed mainly on the endothelial surface of blood vessels and also in the placenta; they both play a key physiologic al role in the protein C anticoagulant pathway. Defects in these proteins m ight play an important role in the pathogenesis of late fetal loss. We perf ormed a case-control study in 95 women with unexplained late fetal loss (>2 0 weeks), to elucidate whether TM or EPCR gene mutations were associated wi th an increased risk for this complication of pregnancy. The control group comprised 236 women who gave birth to at least one healthy baby and had no history of late fetal death or obstetrical complications. The entire TM and EPCR genes, including the promoter region, were screened. In total, five m utations were identified in the TM gene in 95 patients and three in 236 con trol subjects, and two mutations were identified in the EPCR gene in 95 pat ients and one in 236 control subjects. The relative risk for late fetal los s when having a mutation in the TM or EPCR gene was estimated by an odds ra tio of 4.0 (95% CI 1.1-14.9). In conclusion, identified mutations in the TM and EPCR genes of women with unexplained fetal loss are more prevalent com pared with women with no obstetrical complications.