Department of Obstetrics and Gynecology and Center on Health Disparities, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
BMC Med Genet. 2011 May 11;12:64. doi: 10.1186/1471-2350-12-64.
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.
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.
子痫前期影响全球 3-8%的妊娠，是孕产妇和围产儿发病率和死亡率的主要原因。这种复杂的疾病以免疫系统和血管系统的改变为特征，涉及多个器官。有强有力的证据表明子痫前期与遗传因素有关。最近有两项研究报道，内质网氨肽酶 2（ERAP2）基因中的两个不同的单核苷酸多态性（SNPs）与两个不同人群的子痫前期风险增加有关。ERAP2 在胎盘组织中表达，它参与免疫反应、炎症和血压调节；使其成为子痫前期的一个有吸引力的候选基因。此外，ERAP2 的表达在注定要发生子痫前期的女性的早期胎盘组织中发生改变。
采用病例对照设计，检测 ERAP2 基因中的两个 SNPs（rs2549782 和 rs17408150）与 1103 对智利母婴对和 1637 对未配对的非裔美国人样本（836 例母亲，837 例胎儿）中子痫前期状态之间的关联。
我们发现，rs2549782 的胎儿次要等位基因（G）与非裔美国人人群中子痫前期的风险增加相关（P = 0.009），但在智利人群中则不然。我们没有发现 rs17408150 与智利人群子痫前期风险之间的关联。由于该人群中缺乏次要等位基因，因此没有在非裔美国人人群中检测 rs17408150 与子痫前期风险之间的关联。
我们报告了 ERAP2 与非裔美国人子痫前期之间的关联。结合之前在澳大利亚/新西兰人群和挪威人群中发现该基因与母亲有关的研究，ERAP2 现在已与三个人群的子痫前期有关。这有力地证明 ERAP2 在子痫前期的发生中起作用。
