Department of Medicine, PCR Hepatitis Laboratory, Maulana Azad Medical College, University of Delhi, New Delhi, India.
Department of Medical Microbiology, Maulana Azad Medical College, University of Delhi, New Delhi, India.
Indian J Med Res. 2018 Jun;147(6):573-580. doi: 10.4103/ijmr.IJMR_1644_15.
BACKGROUND & OBJECTIVES: Clinical outcome after hepatitis B virus (HBV) exposure varies extremely from spontaneous clearance to chronic hepatitis B and often progresses to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Host genetic factor plays an important role in the regulation of immune response. This study was aimed to investigate whether HLA class II DQA1 and DQB1 gene polymorphism were associated with chronic hepatitis B infection and in the development of HBV-related LC and HCC.
DQA1 and DQB1 allele polymorphism were studied in 187 patients with HBV-related liver diseases (which included 73 chronic hepatitis B, 84 LC and 30 HCC patients) and 109 controls who had spontaneously recovered from HBV infection using polymerase chain reaction amplification with sequence-specific primers.
Our data suggested that DQA10101/2/4 [odds ratio (OR)=2.78; P=0.003], DQA10103 (OR=2.64; P=0.0007) and DQB10302/3 (OR=2.15; P=0.01) were associated with the protection from chronic HBV infection, whereas DQB10402 (OR=0.25; P=0.001) showed susceptible effect on chronic HBV infection. DQB10601 (OR=3.73; P=0.006) conferred protective effect from developing LC; similarly, DQB10302/3 (OR=5.53; P=0.05) and DQB10402 (OR=0.00; P=0.001) conferred protective effect from developing HCC. However, DQA10601 and DQB1*0503 showed susceptible effect on chronic HBV infection; these associations were no longer significant after Bonferroni correction.
INTERPRETATION & CONCLUSIONS: Our results revealed HLA-DQA10101/2/4 - DQA10103 - DQB10302/3 and DQB10601 as protective and DQB1*0402 as risk alleles. The study suggests that various subtypes of HLA-DQA1 and DQB1 are associated with both HBV clearance and development of chronic HBV infections.
乙型肝炎病毒（HBV）暴露后的临床结果差异极大，从自发清除到慢性乙型肝炎不等，且常进展为肝硬化（LC）和肝细胞癌（HCC）。宿主遗传因素在免疫反应的调控中起着重要作用。本研究旨在探讨人类白细胞抗原（HLA）II 类 DQA1 和 DQB1 基因多态性是否与慢性乙型肝炎感染以及 HBV 相关的 LC 和 HCC 的发生有关。
采用聚合酶链反应扩增序列特异性引物，对 187 例 HBV 相关肝病患者（包括 73 例慢性乙型肝炎、84 例 LC 和 30 例 HCC 患者）和 109 例 HBV 感染后自发恢复的对照者进行 DQA1 和 DQB1 等位基因多态性研究。
数据表明，DQA10101/2/4（比值比[OR]=2.78；P=0.003）、DQA10103（OR=2.64；P=0.0007）和 DQB10302/3（OR=2.15；P=0.01）与慢性 HBV 感染的保护作用相关，而 DQB10402（OR=0.25；P=0.001）则与慢性 HBV 感染的易感性相关。DQB10601（OR=3.73；P=0.006）对 LC 的发生具有保护作用；同样，DQB10302/3（OR=5.53；P=0.05）和 DQB10402（OR=0.00；P=0.001）对 HCC 的发生具有保护作用。然而，DQA10601 和 DQB1*0503 对慢性 HBV 感染具有易感性；这些关联在经过 Bonferroni 校正后不再具有统计学意义。
本研究结果表明 HLA-DQA10101/2/4-DQA10103-DQB10302/3 和 DQB10601 为保护性等位基因，而 DQB1*0402 为风险等位基因。研究表明，HLA-DQA1 和 DQB1 的不同亚型与 HBV 清除和慢性 HBV 感染的发展均有关联。
