Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study

A case-control design was used to test for associations between two SNPs in ERAP2, rs2549782 and rs17408150, and preeclampsia status in 1103 Chilean maternal-fetal dyads and 1637 unpaired African American samples (836 maternal, 837 fetal).We found that the fetal minor allele (G) of rs2549782 was associated with an increased risk for preeclampsia in the African American population (P = 0.009), but not in the Chilean population. We found no association between rs17408150 and risk for preeclampsia in the Chilean population. Association between rs17408150 and risk for preeclampsia was not tested in the African American population due to the absence of the minor allele in this population.We report an association between fetal ERAP2 and preeclampsia in an African American population. In conjunction with previous studies, which have found maternal associations with this gene in an Australian/New Zealand population and a Norwegian population, ERAP2 has now been associated with preeclampsia in three populations. This provides strong evidence that ERAP2 plays a role in the development of preeclampsia.Preeclampsia (PE) affects 3-8% of pregnancies worldwide, with rates varying by ethnicity, and leads to potentially devastating complications for both the mother and fetus[1,2]. Preeclampsia is clinically characterized by high blood pressure and proteinuria, usually occurring after 20 weeks of gestation. Although this serious disorder is common during pregnancy, its etiology remains poorly understood[1]. Preeclampsia is considered a disease of the placenta, with shallow trophoblast invasion[3-5] and poor spiral artery remodeling[6-8] being central features of this disorder. It is postulated that immune, vascular, and inflammatory disturbances participate in the placental dysfunction that ultimately produces the preeclampsia phenotype[9].A genetic susceptibility to preeclampsia has been established with both maternal and fetal genes contributing to disease[2,10-17]. Preeclampsia is