HBsAg阳性孕产妇IL28B基因多态性与 HBV宫内感染发生风险关联性分析

The analysis on association between IL28B single gene polymorphisms and the risk of intrauterine infection of HBV in HBsAg positive pregnant women

目的探究HBsAg阳性孕产妇白细胞介素28B(IL28B)基因多态性(SNP)与发生HBV宫内感染的关联性。方法选取单胎足月HBsAg阳性孕产妇为研究对象,并根据是否发生HBV宫内感染分为感染组(658例)与未感染组(1342例),另以542例正常孕妇为对照组。采用四引物扩增受阻突变体系聚合酶链反应(ARMS-PCR)检测IL28B rs8099917位点基因型,采用酶联免疫吸附法(ELISA)检测并比较IL28B rs8099917位点各基因型患者血清IL-17、IL-21、IL-4、转化生长因子-β1(TGF-β1)、γ干扰素(IFN-γ)水平,采用Logistic法分析IL28B rs8099917位点基因型与发生HBV宫内感染的关系。结果 IL28B rs8099917位点存在野生型纯合子TT型、突变杂合子TG型、突变纯合子GG型,且各组中IL28B基因型分布均符合Hardy-weinberg平衡定律。感染组G等位基因频率显著高于T等位基因频率(P<0.05),而未感染组与对照组比较差异无统计学意义(P>0.05);与未感染组、对照组比较,感染组血清IL-17、IL-21、TGF-β1、IL-4水平均显著升高(P<0.05),其中TG与GG型显著高于TT型(P<0.05),且GG型显著高于TG型(P<0.05),而IFN-γ水平显著降低(P<0.05),且GG型显著低于TG与TT型(P<0.05),但未感染组与对照组比较差异无统计学意义(P>0.05)。Logistic分析显示GG基因型为HBV宫内感染发生的危险因素。结论 HBsAg阳性孕产妇IL28B SNP与HBV宫内感染有关,GG基因型可增加HBV宫内感染发生风险。

Objective To investigate the association between interleukin 28B(IL28B)single gene polymorphisms(SNPs)and the risk of intrauterine infection of hepatitis B virus(HBV)in hepatitis B surface antigen(HBsAg)positive pregnant women.Methods Single fetus full-term HBsAg positive pregnant women were selected as the research objects,and were divided into infection group(658 cases)and non-infection group(1342 cases)according to whether HBV intrauterine infection occurred or not,and 542 healthy pregnant women were enrolled as the control group.Tetra-primer amplification refractory mutation system-polymerase chain reaction was used to detect the genotype of IL28B rs8099917 locus,the levels of serum interleukin-17(IL-17),interleukin-21(IL-21),interleukin-4(IL-4),transforming growth factor-β1(TGF-β1)and interferon-γ(IFN-γ)of patients with various genotypes of IL28B rs8099917 locus were measured and compared by enzyme-linked immunosorbent assay,and logistic regression was used to analyze the relationship between IL28B rs8099917 genotype with risk of HBV intrauterine infection.Results There were wild-type homozygous TT genotype,mutant heterozygous TG genotype and mutant homozygous GG genotype of IL28B rs8099917 locus,and the distribution of IL28B genotypes in each group followed Hardy-Weinberg equilibrium law.In infection group,the frequency of G allele was significantly higher than that of T allele(P<0.05),but there was no significant difference in non-infected group and control group(P>0.05).The levels of serum IL-17,IL-21,TGF-β1 and IL-4 in infection group were significantly higher than those in non-infected group and control group(P<0.05).In infection group,the levels in individuals with TG genotype were significantly higher than those with TT genotype(P<0.05),but significantly lower than those with GG genotype(P<0.05),while IFN-γshowed the opposite trend(P<0.05).However,in non-infection and control group,the differences were not significant(P>0.05).Conclusion IL28B SNPs of HBsAg positive pregnant women is related to HBV intrauterine infection,and GG genotype is a risk factor of HBV intrauterine infection.