ABSTRACT

Hepatitis B, caused by hepatitis B virus (HBV) infection, is one of the epidemic and infectious hepatitis diseases. The sigle-nucleotide polymorphisms were identified to associate with HBV infection in East Asian population by genome-wide association study (GWAS), but no study in Yunnan HBV population was reported. We recruited 493 HBV patients and 460 general controls to genotype 7 GWAS SNPs, and then, the association study was performed between these SNPs and biochemical features of HBV patients. The results showed that genotype and allele frequencies of SNPs in the HLA-DP (rs3077, 9277535, and 3128917) and HLA-DQ (rs2856718 and 7453920) genes were associated with HBV infection. Significantly different genotyping frequencies were investigated among three HBV subgroups. Genotype AA of rs3130542 (HLA-C) showed significantly higher frequency in subgroup #1 patients than the other two subgroups (#1 vs. #2, p = .02; #1 vs. #3, p = .03). Meanwhile, genotype frequencies of rs3077, rs9277535, and 3128917 (HLA-DP) were significantly different between patients in subgroup #2 and #3. The indirect bilirubin level was significantly lower in patients with genotype CT of rs3077 than patients with genotype CC (p = .009) or TT (p = .016), and it also showed lower level in patients with genotype GT of rs3128917 than patients with genotype GG (p = .015). The direct bilirubin level was higher in patients with genotype TT of rs4821116 (UBE2L3) than patients with genotype CT (p = .010). In summary, we identified the association between GWAS SNPs and HBV infection or biochemical features in Yunnan HBV population.

摘要

乙型肝炎是由乙型肝炎病毒（HBV）感染引起的乙型肝炎，是一种流行性和传染性肝炎疾病。通过全基因组关联研究（GWAS）确定单核苷酸多态性与东亚人群的HBV感染相关，但没有报道云南HBV人群的研究。我们招募了 493 名 HBV 患者和 460 名普通对照对 7 个 GWAS SNP 进行基因分型，然后对这些 SNP 与 HBV 患者的生化特征进行关联研究。结果表明HLA-DP（rs3077、9277535 和 3128917）和HLA-DQ中 SNP 的基因型和等位基因频率(rs2856718 和 7453920) 基因与 HBV 感染有关。在三个 HBV 亚组中研究了显着不同的基因分型频率。rs3130542 ( HLA-C ) 的基因型 AA在亚组#1 患者中的频率显着高于其他两个亚组（#1 对#2，p = .02；#1 对#3，p = .03）。同时，rs3077、rs9277535和3128917（HLA-DP）的基因型频率在亚组#2和#3的患者之间显着不同。rs3077 基因型 CT 患者的间接胆红素水平显着低于基因型 CC ( p = .009) 或 TT ( p= .016)，并且在 rs3128917 基因型 GT 患者中的水平也低于基因型 GG 患者 ( p = .015)。rs4821116 ( UBE2L3 )基因型TT 患者的直接胆红素水平高于基因型CT 患者( p = .010)。总之，我们确定了云南 HBV 人群中 GWAS SNP 与 HBV 感染或生化特征之间的关联。