A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations
A genome-wide association study identifies polymorphisms in the HLA-DR region associated with non-response to hepatitis B vaccination in Chinese Han populations
复制标题
DOI：
10.1093/hmg/ddt586
复制
发表时间：
2014-04-15
影响因子：
3.5
通讯作者：
Liu, Ying
中科院分区：
文献类型：
--
作者：
Pan, Liping;Zhang, Li;Liu, Ying
接种乙型肝炎疫苗是一种有效的常规做法，可以预防感染。然而，510名健康成年人接种乙肝疫苗后不能产生保护水平的抗体。据报道，宿主基因变异可能影响对乙肝疫苗接种的免疫反应。在这里，我们报道了一项全基因组关联研究，该研究在中国汉族人群中进行，包括108名初次高反应者和77名增强无反应者，他们使用Illumina HumanOmniExpress珠片接种乙肝疫苗。我们鉴定出21个6p21.32位点的snp与乙肝强化疫苗无应答显著相关（p值为110(6)）。该区域最显著的SNP为rs477515，位于HLA-DRB1基因上游12kb处。其p值（4.81 10(8)）超过了bonferroni校正的全基因组显著性阈值。在另外3个汉族人群中验证了捕获这21个snp遗传信息的4个标记snp (rs477515、rs28366298、rs3763316和rs13204672)，其中包括1336个初级高应答者和420个初级无应答者。这四个snp继续显示与乙肝疫苗无应答显著相关(p -联合3.98 10（13)1.42 10(8)）。进一步分析表明，rs477515与乙肝疫苗接种无应答独立相关，校正了我们GWAS中其他三个SNP和以前GWAS中已知的乙肝疫苗免疫相关SNP。我们的研究结果提示rs477515是一个与乙肝疫苗无应答相关的独立标志物，HLA-DR区可能是乙肝疫苗诱导免疫的关键易感位点。
Vaccination against hepatitis B virus is an effective and routine practice that can prevent infection. However, 510 of healthy adults fail to produce protective levels of antibody against the hepatitis B vaccination. It has been reported that host genetic variants might affect the immune response to hepatitis B vaccination. Here, we reported a genome-wide association study in a Chinese Han population consisting of 108 primary high-responders and 77 booster non-responders to hepatitis B vaccination using the Illumina HumanOmniExpress Beadchip. We identified 21 SNPs at 6p21.32 were significantly associated with non-response to booster hepatitis B vaccination (P-value 1 10(6)). The most significant SNP in the region was rs477515, located 12 kb upstream of the HLA-DRB1 gene. Its P-value (4.81 10(8)) exceeded the Bonferroni-corrected genome-wide significance threshold. Four tagging SNPs (rs477515, rs28366298, rs3763316 and rs13204672) that capture genetic information of these 21 SNPs were validated in three additional Chinese Han populations, consisting of 1336 primary high-responders and 420 primary non-responders. The four SNPs continued to show significant associations with non-response to hepatitis B vaccination (P-combined 3.98 10(13) 1.42 10(8)). Further analysis showed that the rs477515 was independently associated with non-response to hepatitis B vaccination with correction for other three SNPs in our GWAS and the known hepatitis B vaccine immunity associated SNP in previous GWAS. Our findings suggest that the rs477515 was an independent marker associated with non-response to hepatitis B vaccination and HLA-DR region might be a critical susceptibility locus of hepatitis B vaccine-induced immunity.