母亲、子代血管紧张素原基因单核苷酸多态性与先兆子痫/子痫的关联研究

Association between both maternal and fetal angiotensinogen gene single nucleotide polymorphism and preeclampsia/eclampsia

目的探讨母亲、子代血管紧张素原(AGT)基因单核苷酸多态性(SNP)与先兆子痫/子痫的关联。方法2008年1月至2015年10月,采用病例-父母/对照-母亲混合研究设计,调查347组病例和700组对照的基本人口学特征,并检测AGT相关SNP的基因型,运用对数线性模型及非条件logistic回归的方法分析母亲、子代AGT各SNP与先兆子痫/子痫的关联。结果当子代rs3789679基因型为GA和AA时,其母亲发生先兆子痫/子痫的风险降低(OR=0.73,95%CI:0.55~0.96;OR=0.62,95%CI:0.39~0.98);当子代rs2493132为TT基因型时,其母亲发生先兆子痫/子痫的风险增加(OR=1.60,95%CI:1.08~2.37),此结果经多重检验校正后无统计学意义。遗传模型分析显示,子代rs3789679在显性模型下(GA+AA/GG)降低了其母亲发生先兆子痫/子痫的风险(OR=0.73,95%CI:0.55~0.96);子代rs2493132在隐性模型(TT/CT+CC)下增加了其母亲发生先兆子痫/子痫的风险(OR=1.66,95%CI:1.13~2.44);母亲rs5051在显性模型下(TC+CC/TT)增加了自身发生先兆子痫/子痫的风险(OR=1.33,95%CI:1.01~1.76)。结论在显性遗传模型下,子代rs3789679GA和AA基因型降低了其母亲发生先兆子痫/子痫的风险,母亲rs5051TC和CC基因型增加了自身发生先兆子痫/子痫的风险。在隐性遗传模型下,子代rs2493132TT基因型增加了其母亲发生疾病的风险。

Objective To explore the association between preeclampsia/eclampsia and maternal and fetal angiotensinogen SNPs. Methods From January 2008 to October 2015, a case-parents/mother-control designed study was conducted among 347 preeclampsia/eclampsia cases and 700 controls to collect related information on their demographic characteristics and to detect the related angiotensinogen SNPs’ genotypes. Both log-linear and unconditional logistic regression methods were employed to investigate the genetic effects of maternal/fetal angiotensinogen SNPs on preeclampsia/eclampsia. Multivariate binary unconditional logistic regression model and covariance were used to analyze the relationship between BMI before pregnancy, weight gain during pregnancy and overweight and obesity in preschool children. Results Both fetal angiotensinogen rs3789679 GA and AA genotype were associated with the reduced risks of preeclampsia/eclampsia, with ORs as 0.73 (95%CI: 0.55-0.96) and 0.62 (95%CI: 0.39-0.98), respectively. For fetal angiotensinogen rs2493132, individuals that carrying the TT genotype, presented a positive association with the risk of preeclampsia/eclampsia, with OR as 1.60 (95%CI: 1.08-2.37). However, these associations were not statistically significant after the correction of the false discovery rate. It was observed that fetal rs3789679 could reduce the risk of preeclampsia/eclampsia (OR=0.73, 95%CI: 0.55-0.96) under the dominant model (GA+AA/GG) while fetal rs2493132 increased the risk of preeclampsia/eclampsia (OR=1.66, 95%CI: 1.13-2.44) under the recessive model (TT/CC+CT). Maternal rs5051 presented an association with preeclampsia/eclampsia (OR=1.33, 95%CI: 1.01-1.76) under the dominant model (TC+CC/TT). Conclusions Results from the dominant model showed that both fetal rs3789679 GA and AA genotype reduced the risk of preeclampsia/eclampsia and maternal rs5051 TC while CC genotype increased the risk of preeclampsia/eclampsia. Fetal rs2493132 TT genotype seemed to be associated with the risk of preeclampsia/eclampsia under the recessive model.