Sun Wenjuan, Xu Yongping, Xin Qian, Zhang Yuan, Cui Baoxia, Hong Fanzhen
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China; Department of Obstetrics, The Second Hospital of Shandong University, Jinan, Shandong, PR China.
Department of Obstetrics, The Second Hospital of Shandong University, Jinan, Shandong, PR China.
Pregnancy Hypertens. 2019 Jan;15:84-92. doi: 10.1016/j.preghy.2018.11.005. Epub 2018 Dec 1.
Cyclophilin A (CypA) plays important roles in inflammation and oxidative stress and is significantly increased in serum of preeclampsia (PE) patients. We aimed to investigate CypA genetic polymorphism and its serum and placenta expressions in severe PE of Han Chinese women.
A case-control study of 82 severe PE patients and 179 healthy pregnancies was conducted. Single-nucleotide polymorphism (SNP) sites of rs3735481, rs9638978 and rs11984372 were analyzed by TaqMan assay. CypA serum levels were determined by enzyme-linked immunosorbent assay (ELISA). CypA mRNA levels and protein expressions in placentas were assessed by quantitative real-time polymerase chain reaction (PCR), western blot, and immunofluorescence assay, respectively.
There were significantly lower frequency of rs3735481 allele C (odds ratio (OR): 0.60, 95% confidence interval (CI): 0.36-0.98; p = .04), and significantly higher frequency of rs9638978 allele A in severe PE especially in early onset PE patients (OR: 2.23, 95% CI: 1.35-3.71, p = .002). Frequency of rs9638978 AA genotype was significantly higher in early onset PE (p < .001). CypA serum levels were significantly higher in severe PE especially in early onset PE (p < .001). Meanwhile, CypA serum levels were significantly lower in carriers with the AC genotype of rs3735481 (p = .019) and significantly higher in carriers with the AA genotype of rs9638978 (p = .017). CypA mRNA levels and protein expressions were found to be significantly increased in PE placentas (both p < .01).
The CypA genetic polymorphisms of rs3735481 and rs9638978 may be associated with severe PE, and rs9638978 AA genotype may be associated with an increasing risk of early onset severe PE in Han Chinese women. High CypA levels in serum and placenta may contribute to the pathogenesis of severe PE. Our results may provide a new clue for the etiology of severe PE.
亲环素A（CypA）在炎症和氧化应激中起重要作用，且子痫前期（PE）患者血清中CypA水平显著升高。我们旨在研究汉族女性重度PE中CypA基因多态性及其血清和胎盘表达。
对82例重度PE患者和179例正常妊娠者进行病例对照研究。采用TaqMan法分析rs3735481、rs9638978和rs11984372的单核苷酸多态性（SNP）位点。采用酶联免疫吸附测定（ELISA）法测定CypA血清水平。分别采用定量实时聚合酶链反应（PCR）、蛋白质印迹法和免疫荧光法评估胎盘组织中CypA mRNA水平和蛋白表达。
重度PE患者中，rs3735481等位基因C的频率显著降低（优势比（OR）：0.60，95%置信区间（CI）：0.36 - 0.98；p = 0.04），而rs9638978等位基因A的频率显著升高，尤其是早发型PE患者（OR：2.23，95% CI：1.35 - 3.71，p = 0.002）。早发型PE患者中rs9638978 AA基因型频率显著更高（p < 0.001）。重度PE患者尤其是早发型PE患者的CypA血清水平显著更高（p < 0.001）。同时，rs3735481 AC基因型携带者的CypA血清水平显著更低（p = 0.019），而rs9638978 AA基因型携带者的CypA血清水平显著更高（p = 0.017）。PE胎盘组织中CypA mRNA水平和蛋白表达均显著升高（均p < 0.01）。
rs3735481和rs9638978的CypA基因多态性可能与重度PE相关，rs9638978 AA基因型可能与汉族女性早发型重度PE风险增加有关。血清和胎盘中高CypA水平可能参与重度PE的发病机制。我们的结果可能为重度PE的病因提供新线索。
