Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas, USA.
Sci Rep. 2020 Mar 16;10(1):4811. doi: 10.1038/s41598-020-60539-9.
Preeclampsia (PE) is a pregnancy specific hypertensive disorder. If untreated PE leads to life threatening condition, eclampsia. Systemic complement activation levels are increased during pregnancy compared to non-pregnant women of childbearing age. In PE, systemic complement levels are further increased, and higher complement deposition has been observed on placentas. We hypothesize that combinations of common SNPs in maternal and fetal complement genes constitute pregnancy specific complotypes and predispose women to PE. In this study, we sequenced two maternal (factor H and C3) and one fetal (CD46) complement genes and identified a total of 9 common SNPs. Minor allele frequencies of two fetal CD46 SNPs were significantly higher in PE. Further, complotypes consisting of fetal CD46 variants and maternal CFH/C3 variants were highly prevalent in PE patients compared to normotensive pregnancies. Placental complement deposition and maternal alternative pathway 50 (AP50) values were higher in PE pregnancies. Irrespective of disease status, two CD46 variants were associated with reduced placental CD46 expression and one CFH variant was associated with increased maternal AP50 values.
子痫前期（PE）是一种妊娠特有的高血压疾病。如果不治疗，PE 会导致危及生命的子痫。与育龄非妊娠妇女相比，妊娠期间全身补体激活水平升高。在 PE 中，全身补体水平进一步升高，并且在胎盘中观察到更高的补体沉积。我们假设母体和胎儿补体基因中的常见 SNP 组合构成妊娠特异性补体型，使女性易患 PE。在这项研究中，我们对两个母体（因子 H 和 C3）和一个胎儿（CD46）补体基因进行了测序，共发现了 9 个常见 SNP。PE 患者中两个胎儿 CD46 SNP 的次要等位基因频率明显更高。此外，与正常妊娠相比，PE 患者中由胎儿 CD46 变体和母体 CFH/C3 变体组成的补体型更为普遍。PE 妊娠时胎盘补体沉积和母体替代途径 50（AP50）值较高。无论疾病状况如何，两个 CD46 变体与胎盘 CD46 表达减少相关，一个 CFH 变体与母体 AP50 值升高相关。
