Li Huihui, Yan Xingyu, Yang Man, Liu Mei, Tian Shan, Yu Mengru, Li Wei-Ping, Zhang Cong
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China.
Int J Hypertens. 2021 Oct 4;2021:3275081. doi: 10.1155/2021/3275081. eCollection 2021.
Preeclampsia (PE) is a severe complication in pregnancy and a leading cause of maternal and infant mortality. However, the exact underlying etiology of PE remains unknown. Emerging evidence indicates that the cause of PE is associated with genetic factors. Therefore, the aim of this study is to identify susceptibility genes to PE.
Human Exome BeadChip assays were conducted using 370 cases and 482 controls and 21 loci were discovered. A further independent set of 958 cases and 1007 controls were recruited for genotyping to determine whether the genes of interest and are associated with PE. Immunohistochemistry was used for localization. Both qPCR and Western blotting were utilized to investigate the levels of PTPRK in placentas of 20 PE and 20 normal pregnancies.
The allele frequency of rs3190930 differed significantly between PE and controls and was particularly significant in severe PE subgroup and early-onset PE subgroup. PTPRK is primarily localized in placental trophoblast cells. The mRNA and protein levels of PTPRK in PE were significantly higher than those in controls.
These results suggest that PTPRK appears to be a previously unrecognized susceptibility gene for PE in Han Chinese women, and its expression is also associated with PE, while rs9489124 has no apparent correlation with PE risk.
子痫前期（PE）是妊娠期一种严重的并发症，是母婴死亡的主要原因。然而，PE确切的潜在病因仍不清楚。新出现的证据表明，PE的病因与遗传因素有关。因此，本研究的目的是确定PE的易感基因。
使用370例病例和482例对照进行人类外显子芯片检测，发现了21个基因座。另外招募了958例病例和1007例对照的独立样本进行基因分型，以确定感兴趣的基因是否与PE相关。采用免疫组织化学进行定位。运用qPCR和蛋白质印迹法研究20例PE妊娠和20例正常妊娠胎盘组织中PTPRK的水平。
rs3190930的等位基因频率在PE组和对照组之间存在显著差异，在重度PE亚组和早发型PE亚组中尤为显著。PTPRK主要定位于胎盘滋养层细胞。PE组中PTPRK的mRNA和蛋白水平显著高于对照组。
这些结果表明，PTPRK似乎是汉族女性中一种先前未被认识的PE易感基因，其表达也与PE相关，而rs9489124与PE风险无明显相关性。
