华南汉族女性TNF-α基因多态与早产的相关研究

Study on correlation between gene polymorphism of tumor necrosis factor-α and preterm delivery in women of Han nationality in Southern China

目的:研究肿瘤坏死因子(tum or necrosis facor,TNF)-α基因-308、+488位点单核酸多态性(single nucleotide polym orphism,SNP)与华南地区汉族女性早产的相关性,并探讨其与早产相关危险因素的交互作用。方法:应用病例对照研究方法,选取116例正常足月产妇及110例早产产妇为研究对象,采用聚合酶链反应-高分辨率熔解曲线(PCR-HRM)技术结合测序法检测其TNF-α基因-308、+488位点多态性分布,运用多因素Logistic回归等方法分析基因型和早产的关系以及与相关危险因素的交互作用。结果:①检测到对照组和早产组的TNF-α基因-308位点基因型GG、GA、AA频率分布均为84.5%、15.5%和0%,+488位点基因型GG、GA、AA频率分别为78.5%、19.8%、1.7%和69.1%、28.2%、2.7%,两组基因型分布频率和等位基因频率比较差异无统计学意义(P>0.05)。②TNF-α基因产妇有家族早产史、孕期阴道炎、胎膜早破为早产的危险因素,TNF-α基因-308位点GA基因型对家族早产史、孕期阴道炎、胎膜早破的暴露效应有放大作用,+488位点GA+AA基因型对胎膜早破、家族早产史的暴露效应也有放大作用,交互作用系数(r)均>1,均为超相乘交互模型。结论:TNF-α基因+488位点GA+AA基因型和-308位点GA基因型与华南汉族女性早产的危险性相关,且与胎膜早破、家族早产史存在一定的交互作用。

Objective：To study the correlation between single nucleotide polymorphism（SNP） of tumor necrosis factor-α（TNF-α） gene-308 and ＋488 locus and preterm delivery in women of Han nationality in Southern China,and explore the its interaction with related risk factors of preterm delivery.Methods：116 normal full term pregnant women and 110 pregnant women of preterm delivery were selected as study objects by case-control study,polymerase chain reaction-high resolution melting curve（PCR-HRM） combined with gene sequencing were used to detect the polymorphic distribution of TNF-α gene-308 and ＋488 locus,and multivariate logistic regression analysis was used to analyze the relationship between genotype and preterm delivery as well as their interaction with related risk factors.Results：The frequencies of GG,GA,AA genotypes in TNF-α gene-308 locus in control group and preterm delivery group were 84.5%,15.5% and 0%,respectively;the frequencies of GG,GA,AA genotypes in TNF-α gene＋488 locus in control group and preterm delivery group were 78.5%,19.8%,1.7% and 69.1%,28.2%,2.7%,respectively,there was no significant difference in frequencies of genotype and allele between the two groups（P 0.05）;for the pregnant women with TNF-α,the family history of preterm delivery,vaginitis during pregnancy and premature rupture of fetal membranes were risk factors of preterm delivery,GA genotype in TNF-α gene-308 locus amplified the effects of family history of preterm delivery,vaginitis during pregnancy and premature rupture of fetal membranes;GA genotype and AA genotype in TNF-α gene＋488 locus amplified the effects of family history of preterm delivery and premature rupture of fetal membranes;interaction indexes（r） were greater than 1,both being multiplicative interaction model.Conclusion：GA genotype and AA genotype in TNF-α gene＋488 locus and GA genotype in TNF-α gene-308 locus are related to preterm delivery in women of Han nationality in Southern China,and a certain interaction exists between them and premature rupture of fetal membranes,family history of preterm delivery.