IFN-γ+874基因单核苷酸多态性与宫内HBV感染易感性关系的研究

目的　研究宫内乙型肝炎病毒 (HBV)感染患儿的干扰素γ(IFN γ) 874单核苷酸多态性 (SNP)与宫内HBV感染易感性的关系 ,探讨宫内HBV感染的遗传易感因素。方法　母亲为HBV携带者 ,新生儿出生后按程序使用乙肝疫苗或乙肝疫苗联合乙肝免疫球蛋白进行免疫。出生时外周静脉血HBsAg和 (或 )HBV DNA阳性并持续阳性 6个月以上者为宫内HBV感染组 ,共 4 6例。出生时及以后随访中未曾出现过HBsAg或HBV DNA阳性 ,1岁时抗HBs达保护滴度以上者为正常免疫组 ,共73例。用ABIPrism770 0高通量荧光PCR系统对IFN γ 874SNP进行测定。结果　宫内HBV感染组IFN γ 874AA、AT和TT基因型分布频率分别为 6 7 4 %、19 6 %和 13 0 % ;正常免疫组AA、AT和TT基因型分布频率分别为 4 5 2 %、30 1%和 2 4 7%。两组IFN γ 874基因型的分布频率差异有显著性 (χ2=5 10 2 ,P <0 0 5 )。宫内HBV感染儿童IFN γ 874AA基因型占优势。结论IFN γ 874基因多态性与宫内HBV感染有关 ,提示IFN γ 874基因多态性可能在决定个体宫内HBV感染遗传易感性方面有一定意义

Association of interferon-gamma + 874 gene single nucleotide polymorphism with susceptibility to intrauterine HBV infection

OBJECTIVE: To explore the susceptibility of children to develop intrauterine hepatitis B virus (HBV) infection through studying the association between interferon gamma (IFN-gamma) + 874 single nucleotide polymorphism (SNP) and intrauterine HBV infection. METHODS: The subjects were selected from outpatients who were in our hepatitis B (HB) vaccine following-up clinics. The subjects whose mothers were HBV carriers were inoculated with HB vaccine or HB vaccine and hepatitis B immunoglobulin (HBIg). Intrauterine HBV infection was defined as peripheral blood HBsAg and/or HBV-DNA positive at birth and lasting for six months (group I). Normal immune children were defined as peripheral blood negative for HBV marker since birth and afterwards HBsAb titers were above protective level (group II). The subjects were composed of the following two groups. Group I consisted of 46 children with intrauterine HBV infection. Group II was composed of 73 normal children. A Taqman fluorescence polymerase chain reaction for the IFN-gamma + 874 SNP was performed for both groups. RESULTS: IFN-gamma + 874 SNP was tested successfully for every subject. Frequencies of AA, AT and TT genotype were 67.4%, 19.6% and 13.0% in the intrauterine HBV infection group, and 45.2%, 30.1% and 24.7% in the normal immune children group. A significant difference was found in the frequency distribution of IFN-gamma + 874 genotype between the two groups (chi(2) = 5.102, P = 0.02389). In the intrauterine HBV infection group the AA genotype was more common than in normal immune group. CONCLUSION: There is an association between IFN-gamma + 874 SNP and intrauterine HBV infection. This study suggested the possibility that IFN-gamma + 874 SNP might be important in determining an individual's susceptibility to development of intrauterine HBV infection.