广西苗族、侗族儿童乙肝疫苗初次免疫应答水平与TLR基因多态性的关联

Correlation between hepatitis B vaccine primary immune response level and TLR gene polymorphism in Miao and Dong children in Guangxi

目的探讨广西苗族、侗族儿童乙肝疫苗初次免疫应答水平与TLR基因多态性的关联,为了解乙肝疫苗低/无应答的遗传学机制提供依据。方法收集2014-2016年到广西融水县人民医院、三江县人民医院儿科就诊的8~9月龄苗族儿童293例、侗族儿童279例为研究对象。采集各研究对象外周静脉血,检测乙肝血清标志物(HBs Ag、抗-HBs、HBe Ag、抗-HBe、抗-HBc)和HBV DNA等指标,应用SNPscan TM多重SNP分型技术检测TLR基因10个位点的基因多态性,采用多元线性回归分析TLR等位基因、基因型与抗-HBs水平的关联。结果 TLR2基因rs3804100位点和TLR3基因rs13126816位点的基因多态性与广西苗族儿童初次乙肝疫苗免疫后抗-HBs水平有关(P<0. 05),TLR3其余SNPs、TLR4的SNPs均与苗族儿童乙肝疫苗免疫应答无关(P>0. 05)。TLR2、TLR3和TLR4基因多态性与广西侗族儿童初次乙肝疫苗免疫后抗-HBs水平均无关联(P>0. 05)。TLR2基因rs3804100位点T/T基因型和C/T基因型儿童的抗-HBs水平明显高于C/C基因型的儿童,差异均有统计学意义(P<0. 05);携带等位基因T儿童的抗-HBs水平也明显高于携带等位基因C的儿童,差异有统计学意义(P <0. 05)。TLR3基因rs13126816位点A/A基因型和G/A基因型儿童的抗-HBs水平明显低于G/G基因型的儿童,差异均有统计学意义(P<0. 05);携带等位基因A儿童的抗-HBs水平也明显低于携带等位基因G的儿童,差异有统计学意义(P<0. 05)。结论 TLR2基因rs3804100位点的等位基因C和TLR3基因rs13126816位点等位基因A可能会降低苗族儿童产生初次乙肝疫苗免疫应答的水平。

Objective To explore the correlation between hepatitis B vaccine primary immune response level and TLR gene polymorphism in Miao and Dong children in Guangxi,provide a basis for researching the genetic mechanism of low/no response of hepatitis B vaccine.Methods A total of 293 Miao children and 279 Dong children aged 8-9 months were collected from Department of Pediatrics in Rongshui County People’s Hospital and Sanjiang County People’s Hospital from 2014 to 2016.Peripheral venous blood samples were collected to detect HBV serum markers(HBs Ag,anti-HBs,HBe Ag,anti-HBe,anti-HBc)and HBV DNA.SNPscan TM multiple SNP typing technique was used to detect polymorphisms of 10 loci of TLR gene.Multiple linear regression analysis was used to analyze the correlations between TLR alleles,genotypes and anti-HBs levels.Results Gene polymorphisms of TLR2 gene rs3804100 locus and TLR3 gene rs13126816 locus were related to levels of anti-HBs after primary immune response of hepatitis B vaccine in Miao children in Guangxi(P<0.05).The rest of SNPs of TLR3 genes and all TLR4 genes were not related to immune response of hepatitis B vaccine in Miao children(P>0.05).TLR2,TLR3,and TLR4 gene polymorphisms were not related to anti-HBs levels after primary immune response of hepatitis B vaccine in Dong children in Guangxi(P>0.05).The levels of anti-HBs in children with T/T genotype and C/T genotype of TLR2 gene rs3804100 locus were statistically significantly higher than those in children with C/T genotype of TLR2 gene rs3804100 locus(P<0.05).The levels of anti-HBs in children with T allele were statistically significantly higher than those in children with C allele(P<0.05).The levels of anti-HBs in children with A/A genotype and G/A genotype of TLR3 gene rs13126816 locus were statistically significantly lower than those in children with G/G genotype of TLR3 gene rs13126816 locus(P<0.05).The levels of anti-HBs in children with A allele were statistically significantly lower than those in children with G allele(P<0.05).Conclusion C allele of TLR2 gene rs3804100 locus and A allele of TLR3 gene rs13126816 locus may reduce the level of primary immune response of hepatitis B vaccine in Miao children.