细胞因子基因多态性与乙型肝炎病毒宫内感染易感性的研究

Relationship between cytokine gene polymorphism and susceptibility to hepatitis B virus intrauterine infection

目的对前期研究发现宫内乙型肝炎病毒(HBV)感染免疫失败儿童表达异常的细胞因子TNFα、IFNγ、IL4和IL10,研究其相关基因位点单核苷酸多态性与HBV宫内感染易感性的关系。方法在确定时限内选择乙型肝炎疫苗随访门诊中符合纳入标准的高危儿童,系宫内感染HBV经免疫接种失败者为Ⅰ组,免疫接种有效者为Ⅱ组和非携带HBV母亲所生健康儿童作对照。应用实时荧光定量PCR技术检测TNFα基因-238位点、IFNγ基因+874位点、IL4基因-590位点和IL10基因-1082位点的单核苷酸多态性。结果TNFα基因-238位点A等位基因频率Ⅰ组显著高于Ⅱ组(χ2=6.797,P<0.05),并与对照组相比较差异有显著性(χ2=9.513,P<0.05),而Ⅱ组与对照组比较χ2=0.047,P>0.05;IFNγ基因+874位点A基因频率Ⅰ组与Ⅱ组比较χ2=7.238,P<0.05,与对照组比较χ2=5.199,P<0.05,Ⅱ组与对照组比较χ2=0.602,P>0.05;IL4基因-590位点C/T等位基因频率Ⅰ组与Ⅱ组比较χ2=0.632,P>0.05,Ⅰ组与对照组比较χ2=0.584,P>0.05,Ⅱ组与对照组比较χ2=0.004,P>0.05;IL10基因-1082位点G等位基因频率Ⅱ组与Ⅰ组比较χ2=10.359,P<0.001,Ⅱ组与对照组比较χ2=35.418,P<0.001,但是Ⅰ组与对照组比较差异无显著性(χ2=1.759,P>0.05)。

Objective To explore the possible relationship between cytokines(TNF-α?IFN-γ?IL-4 and IL-10),which were expressed abnormal quantity in the peripheral blood to intrauterine HBV infectious children,gene single nucleotide polymorphism(SNP) and susceptibility to HBV intrauterine infection. Methods A cross sectional study on molecular epidemiology was carried out. The subjects were selected from outpatients of the hepatitis B vaccine special clinics of our hospital. According to intrant criteria,children under high risk of HBV intrauterine infection were divided into immuno-failure group (group Ⅰ) and immuno-effective group (group Ⅱ) while children without high risk were included in the control group. Four gene SNP sites of TNF-α-238?IFN-γ +874?IL-4-590 and IL-10-1082 region were determined by real-time quantitative fluorescent PCR. Results Significant differences of TNF-α -238 A allele frequency were found between group Ⅰ and groupⅡ (χ2=6.797,P<0.05) as well as between groupⅠ and control group(χ2=9.513,P<0.05).No evident difference of TNF-α-238 A was found between group Ⅱ and control group (χ2=0.047,P>0.05). Significant differences of IFN-γ +874 A allele frequency were found between group Ⅰ and group Ⅱ(χ2=7.238,P<0.05),and between groupⅠ and the controls (χ2=5.199,P<0.05) but no significant difference was found between groupⅡ and control group (χ2=0.602,P>0.05). Significant differences of IL-4-590 C/T allele frequency were not found between groupⅠand group Ⅱ( χ2= 0.632 , P> 0.05 ), groupⅠ and control group ( χ2= 0.584 , P> 0.05 ),or between group Ⅱ and control group ( χ2= 0.004 , P> 0.05 ) respectively. Significant differences of IL-10-1082 G allele frequency were found between group Ⅱ and group Ⅰ (χ2=10.359, P< 0.001 ),and between group Ⅱ and the controls ( χ2= 35.418 , P< 0.001 ),but not found between groupⅠand control group ( χ2= 1.759 , P> 0.05 ). Conclusion This study suggested the possibility that TNF-α -238 A allele and IFN-γ +874 A allele were associated with HBV intrauterine infection.There was no evident relationship between IL-4-590 C/T allele SNP and susceptibility to HBV intrauterine infection,but the IL-10-1082 G allele seemed to be associated with prenentive efficacy to HBV intrauterine infection.