摘要
目的:了解子痫前期(PE)易感基因多态性(SNP)在中国人群中的分布特点,探讨SNP与PE遗传易感性之间的关系;应用多因子降维法(MDR)分析SNPs的交互作用,以期建立PE的多基因预测模型用于疾病风险的评估。方法:收集深圳地区中国汉族PE患者156例与正常妊娠妇女286例,Snap Shot技术进行基因型鉴定,用卡方检验进行单位点关联分析,MDR法分析基因-基因交互作用;并构建多位点logistic模型。结果:(1)经Buffarrony校正后,e NOS基因rs2070744等位基因频率分布在中国汉族人群中有统计学差异,PE组"C"等位基因频率明显高于对照组(C vs T:χ~2=8.852,P=0.003)。(2)中国汉族人群中暂未发现rs1800580、rs5742620、rs6020、rs1799963、rs1799889、rs4986791、rs4986790、rs268位点存在多态性。(3)最佳交互作用模型包含EPAP2(rs2549782)、GSTP1(rs1695)、AGT(rs4762)、IL-10(rs1800896)、APOE(rs7412)和TNF-alpha(rs1800629、rs1799724)。训练样本准确率为0.7294,验证样本准确率为0.5853,交叉验证一致性为10/10(P=0.001)。(4)基于MDR结果构建的logistic回归模型结果显示,rs1800896、rs1799724、rs2070744、rs4762及rs7412位点有统计学意义。结论:中国汉族人群PE风险遗传因素具有人种特异性;MDR方法是对PE的多因素效应估计的新尝试,6个PE易感基因存在交互作用,可能对中国人群PE的发病起重要作用。
Objective：To investigate the distribution characteristics of genetic polymorphisms in Chinese-Han population and to identify the interactions of susceptive genes with related to the genetic polymorphism and their impacts on the risk of pre-eclampsia（PE）by using Multifactor Dimensionality Reduction（MDR）model.Methods：A total of 442 cases of PE patients as well as normal pregnant women in Shenzhen Maternity and Child Healthcare Hospital from July 2014 to May 2015 were selected.Genotyping was performed using Snap Shot and data were statistically analyzed by chi-square test,MDR and Logistic regression analysis.Results：（1）The frequency of polymorphisms（rs2070744）in e NOS was significantly different between patients with PE and controls after Buffarrony correction in Chinese Han population.The＂C＂allele frequency of rs2070744 in research group was significantly increased than that in control group（C vs T：χ~2=8.852,P=0.003）.（2）The SNPs of rs1800580,rs5742620,rs6020,rs1799963,rs1799889,rs4986791,rs4986790 and rs268 had not been detected in pregnant Chinese-Han women.（3）Results of MDR interaction analysis showed that the optimal model included rs2549782,rs1695,rs4762,rs1800896,rs7412,and rs1800629,rs1799724.（4）5 loci included rs1800896,rs1799724,rs2070744,rs4762 and rs7412 showed significant value in logistic regression analysis on account of MDR results.Conclusion：PE has a strong genetic factor in its causes,and shows a complex process of the interactions of various factors.6 genes had interactions,which may play an important role in the pathogenesisof PE.The MDR model may be an effective method for estimating risks of PE.
出处
《现代妇产科进展》
CSCD
北大核心
2018年第1期1-5,共5页
Progress in Obstetrics and Gynecology
基金
广东省医学科研基金(No:A2016285)
深圳市科技研发资金(No:JCYJ20150402090413006)
