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Title: [Association of HLA-DQ and IFNL4 polymorphisms with hepatitis B virus infection and clearance].
Author: Chen H, Fan JH, Chen WX, Guo JJ, Huang Y.
Journal: Zhonghua Gan Zang Bing Za Zhi; 2017 Jul 20; 25(7):506-511. PubMed ID: 29055988.
Abstract:
Objective: To confirmed the polymorphisms of HLA-DQ and IFNL4 were associated with HBV infection and clearance in a Chinese population. Methods: The Sequenom MassARRAY MALDI-TOF system was used to genotype the HLA-DQrs9275319 and IFNL4rs368234815, rs12971396, rs12979860, and rs8099917. A binary logistic regression test was conducted to estimate the relative risk of these SNPs with HBV infection and clearance. Haploview4.2 software and PHASE software (v2.0.2) were employed to analyze linkage disequilibrium (LD) and haplotype frequencies. The MDR program was applied to analyze interactions between SNP and SNP.Statistical analysis was performed using SPSS 19.0 and P-values were corrected by Bonferroni's corrections. Results: A total of 1,069 subjects were recruited and divided into three groups: 238 healthy controls(HC), 397 with HBV-related chronic liver disease (CLD), 434 with spontaneous clearance (SC). The rs9275319TT was most frequently identified among all groups(86.2% in the CLD group, 77.6% in the SC group, and 75.9% in the HC group).Carriage of the rs9275319 C allele was a protective factor for chronic HBV infection (the allele model: P = 0.000 3, OR,0.514; 95% CI, 0.359-0.738) and clearance (the allele model: P = 0.002, OR, 1.659; 95% CI, 1.197-2.300). HLA-DQ rs9275319 showed a significant association with HBV infection (allele model, OR, 0.514; 95% CI, 0.359-0.738, adjusted P = 0.000 3) and spontaneous clearance (allele model, OR, 1.659; 95% CI, 1.197-2.300, adjusted P = 0.002). However, there was no association between IFNL4 polymorphism and HBV infection((allele model: P = 0.082 for rs368234815; P = 0.063 for rs12971396; P = 0.517 for rs12979860; P =0.695 for rs8099917) or spontaneous clearance ((allele model: P = 0.358 for rs368234815; P = 0.105 for rs12971396; P = 0.640 for rs12979860; P = 0.640 for rs8099917;all P > 0.05). The multifactor dimensionality reduction (MDR) test showed there was a three-way interaction (rs12971396, rs12979860, and rs9275319) between IFNL4 and HLA-DQ polymorphisms for HBV infection (permutation P = 0.009 for the best factor model) and clearance (permutation P = 0.014 for the best factor model). Conclusion: The SNP-SNP interaction between HLA-DQ and IFNL4 is associated with the regulation of HBV infection and natural clearance. 目的： 研究人类白细胞抗原DQ（HLA-DQ）和干扰素λ4（IFN-L4）的基因多态性与中国汉族人群乙型肝炎病毒（HBV）感染和清除的相关性。 方法： 用Sequenom MassARRAY MALDI-TOF系统对HLA-DQ基因多态性位点rs9275319和IFN-L4基因多态性位点rs368234815、rs12971396、rs12979860、rs8099917进行分型。用logistic回归分析评估单核苷酸多态性(SNP)与HBV感染风险和自发清除的关系。用Haploview4.2软件和PHASE软件分析连锁不平衡和单体型频率。采用多因素降维法分析SNP-SNP之间的相互作用。所有结果均用SPSS19.0软件进行统计学分析和Bonferroni校正。 结果： 本研究纳入的受试者分别为：健康对照组238例、HBV相关慢性肝病组397例和乙型肝炎感染后自发清除组434例，共计1 069例。在HLA-DQ基因多态性位点rs9275319中，rs9275319 TT在各组中最常见（HBV相关慢性肝病组86.2%、自发清除组77.6%和对照组75.9%）；而rs9275319 C等位基因是HBV感染（等位基因模型P = 0.000 3；OR：0.514；95% CI：0.359~0.738）和清除（等位基因模型P = 0.002；OR：1.659；95% CI：1.197~2.300）的保护性因素。HLA-DQ rs9275319与HBV的易感性（等位基因模型OR：0.514；95%CI：0.359~0.738；校正后P = 0.000 3）和自发清除（等位基因模型OR：1.659；95% CI：1.197~2.300；校正后P = 0.002）有很强的相关性。IFN-L4基因多态性与HBV的易感性(等位基因模型：rs368234815，P = 0.082；rs12971396，P = 0.063；rs12979860，P = 0.517；rs8099917，P = 0.695)和自发清除不相关（等位基因模型：rs368234815,P = 0.358；rs12971396，P = 0.105；rs12979860，P = 0.640；rs8099917，P = 0.640；P值均> 0.05）。多因素降维法分析结果显示，在HBV易感性（最佳因子模型P = 0.009）和自发清除（最佳因子模型P = 0.014）中，IFN-L4（rs12971396、rs12979860）和HLA-DQ（rs9275319) SNP有三方互动作用。 结论： HLA-DQ和IFN-L4基因SNP-SNP间的相互作用与HBV感染和自发清除调节有关。.

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