Abstract
BackgroundPreeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide. This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. There is strong evidence for a genetic contribution to preeclampsia. Two different single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene were recently reported to be associated with increased risk for preeclampsia in two different populations. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate gene. Furthermore, ERAP2 expression is altered in first trimester placentas of women destined to develop preeclampsia.MethodsA 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).ResultsWe 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.ConclusionsWe 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.
Highlights
Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide
Our results demonstrate that the rs2549782 single nucleotide polymorphisms (SNPs) of the fetal endoplasmic reticulum aminopeptidase 2 (ERAP2) gene is significantly associated with risk for preeclampsia in the African American population; further suggesting that this gene plays a key role in the development of disease and may provide insight into the disparity between preeclampsia rates between ethnic groups
Significant differences in fetal sex have been reported in the literature, but results vary with some studies reporting a bias towards male fetuses, some reporting a bias towards female fetuses, and still others reporting no differences in fetal sex in association with preeclampsia[36,37,38,39,40,41,42,43,44]
Summary
Preeclampsia affects 3-8% of pregnancies and is a major cause of maternal and perinatal morbidity and mortality worldwide This complex disorder is characterized by alterations in the immune and vascular systems and involves multiple organs. ERAP2 is expressed in placental tissue and it is involved in immune responses, inflammation, and blood pressure regulation; making it is an attractive preeclampsia candidate gene. Preeclampsia is clinically characterized by high blood pressure and proteinuria, usually occurring after 20 weeks of gestation This serious disorder is common during pregnancy, its etiology remains. The involvement of ERAP2 in multiple pathways known to influence the risk for preeclampsia, its expression in placental tissue, and the previously described altered expression of ERAP2 in placentas before maternal symptoms developed[29]; suggest that the fetal ERAP2 gene contributes to the development of preeclampsia
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