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Background  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. 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.    Methods  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).    Results  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.    Conclusions  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.

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