Fan Jia-Hao, Hou Si-Hui, Qing-Ling Li, Hu Jun, Peng Hong, Guo Jin-Jun
Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
Ann Hepatol. 2016 Jul-Aug;15(4):532-9.
Background and aim. Leukocyte antigen DQ (HLA-DQ) and interferon-λ4 (IFNL4) gene polymorphisms were associated with susceptibility to chronic hepatitis B and C virus infection. This study further confirmed that variants of these genes were associated with susceptibility and spontaneous clearance of HBV infection in a Chinese population.
A total of 1,069 subjects were recruited and divided into three groups i.e. 397 with CLD (HBV-related chronic liver disease), 434 with SC (spontaneous clearance), and 238 HC (healthy controls). HLA-DQrs9275319 and IFNL4rs368234815, rs12971396, rs12979860, and rs8099917SNPs were genotyped using the Sequenom MassARRAY MALDI-TOF system.
HLA-DQ rs9275319 showed a significant association with HBV infection (allele model, OR, 0.514; 95% CI, 0.359-0.738, adjusted p = 0.0003) and with natural clearance (allele model, OR, 1.659; 95% CI, 1.197-2.300, adjusted. However, there was no association between IFNL4 polymorphism and HBV susceptibility or natural clearance (all p > 0.05). The multifactor dimensionality reduction (MDR) test with permutation correction showed that a three-way interaction between IFNL4 and HLA-DQ SNPs was identified for HBV susceptibility (permutation p = 0.009 for the best factor model) and clearance (permutation p = 0.014 for the best factor model).
The data from the current study provided additional evidence for an SNP-SNP interaction between HLA-DQ and IFNL4 in regulation to HBV infection and natural clearance.
背景与目的。白细胞抗原DQ(HLA - DQ)和干扰素λ4(IFNL4)基因多态性与慢性乙型和丙型肝炎病毒感染的易感性相关。本研究进一步证实这些基因的变异与中国人群中HBV感染的易感性和自发清除相关。
共招募1069名受试者,分为三组,即397例慢性肝病患者(HBV相关慢性肝病)、434例自发清除者(SC)和238例健康对照(HC)。使用Sequenom MassARRAY MALDI - TOF系统对HLA - DQ rs9275319以及IFNL4 rs368234815、rs12971396、rs12979860和rs8099917单核苷酸多态性(SNP)进行基因分型。
HLA - DQ rs9275319与HBV感染显著相关(等位基因模型,比值比[OR]为0.514;95%置信区间[CI]为0.359 - 0.738,校正p = 0.0003),与自然清除也显著相关(等位基因模型,OR为1.659;95% CI为1.197 - 2.300,校正后)。然而,IFNL4多态性与HBV易感性或自然清除之间无关联(所有p > 0.05)。经置换校正的多因素降维(MDR)检验表明,IFNL4与HLA - DQ SNP之间的三向相互作用与HBV易感性(最佳因子模型的置换p = 0.009)和清除(最佳因子模型的置换p = 0.014)相关。
本研究数据为HLA - DQ和IFNL4之间在调节HBV感染和自然清除方面的单核苷酸多态性 - 单核苷酸多态性相互作用提供了更多证据。