TLR基因多态性对广西汉族儿童乙型肝炎疫苗初次免疫应答水平的影响

  目的  探讨Toll样受体(toll-like receptors，TLR)基因多态性与广西汉族儿童乙型肝炎(以下简称乙肝)疫苗初次免疫应答水平的关联。  方法  收集2014-2016年到广西自治区妇幼保健院、南宁市妇幼保健院儿科就诊的8~9月龄汉族儿童513例为研究对象。采集外周血标本，采用微粒子酶免疫法检测乙肝血清标志物"两对半"，用套式聚合酶链式反应法检测乙肝病毒DNA，应用SNPscanTM多重SNP分型技术检测TLR基因10个位点的基因多态性。采用非条件Logistic回归分析TLR等位基因、基因型与儿童乙肝疫苗免疫后应答的关联。  结果  TLR3基因rs13126816的基因多态性与广西汉族儿童初次乙肝疫苗免疫后应答情况有关(OR=1.79，95% CI:1.11~2.89，P=0.018)；A/A基因型[238.04(519.75) mIU/L]和G/A基因型[347.96(619.68) mIU/L]儿童的乙肝病毒表面抗体(hepatitis B surface antibody，抗-HBs)水平明显低于G/G基因型[489.08(854.76) mIU/L]的儿童，差异均有统计学意义(均有P < 0.05)；携带等位基因A[317.20(608.72) mIU/L]儿童的抗-HBs水平也明显低于携带等位基因G[457.01(852.66) mIU/L]的儿童，差异有统计学意义(Z=-3.055，P < 0.05)。TLR基因其余位点均与乙肝疫苗免疫应答无关(均有P>0.05)。  结论  TLR3基因rs13126816位点等位基因A可能是汉族儿童产生初次乙肝疫苗免疫低应答的影响因素。

Effect of TLR gene polymorphisms on primary immune response to hepatitis B vaccine in Han children of Guangxi

  Objective  To explore the association between Toll-like receptors(TLR) gene polymorphisms and the primary immune response level to Hepatitis B Vaccine in Han children in Guangxi.  Methods  A total of 513 Han children aged 8-9 months were collected from the department of pediatrics in the Maternal and Child Hospital of Guangxi Zhuang Autonomous Region and Nanning Maternal and Child Health Hospital from 2014 to 2016. Peripheral venous blood of each study object was collected to detect HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc and HBV DNA. The polymorphisms of 10 sites of TLR gene were detected by SNPscanTM multiple SNP typing techniques. The association between allele, genotype of TLR gene and anti-HBs levels were analyzed by non-conditional logistic regression.  Results  The genetic polymorphism of TLR3 gene rs13126816 was related to immune response after primary Hepatitis B immunization in Han children in Guangxi (OR=1.79, 95% CI: 1.11-2.89, P=0.018). The anti-HBs level of children with A/A genotype[238.04(519.75) mIU/L] and G/A genotype[347.96(619.68) mIU/L] were significantly lower than those with G/G genotype[489.08(854.76) mIU/L], and the differences were statistically significant (all P < 0.05). Anti-HBs level of children carrying allele A[317.20(608.72) mIU/L] was significantly lower than those carrying allele G[457.01(852.66) mIU/L], and the difference was statistically significant (Z=-3.055, P < 0.05). The rest of the TLR genes were not related to the immune response of Hepatitis B Vaccine (all P>0.05).  Conclusions  The allele A of TLR3 gene rs13126816 may be the influencing factor for the low response of primary immune response to Hepatitis B Vaccine in Han children.