Persistent effect of IFNAR-1 genetic polymorphism on the long-term pathogenesis of chronic HBV infection.
Genetic polymorphism of IFNAR-1 plays a large role in determining the clearance or chronicity after hepatitis B virus (HBV) exposure. However, it is not clear whether type I interferon receptor-1 (IFNAR-1) variations continuously exert their effects to influence the final outcomes following HBV chronicity, including acute-on-chronic hepatitis B liver failure (ACLF-HBV), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Here we report that these four potential outcomes of chronic HBV infection are strongly associated with IFNAR-1 polymorphisms through a hospital-based case-control study of 663 cases. ACLF-HBV and HCC were each compared with CHB+LC. In comparison with the G/G genotype, the C/G and C/C genotypes at both single-nucleotide polymorphism (SNP) sites (rs1012335 and rs2257167) showed significant susceptibility to ACLF-HBV (the highest odds ratio [OR] reached 2.374; 95% CI = 1.488, 3.788; p < 0.001 for the C/G genotype at rs2257167), as well as HCC (OR = 2.475; 95% CI = 1.435, 4.426; p < 0.001 for the C/C genotype at rs1012335). The C allele at both loci was a susceptibility allele for ACLF-HBV and HCC, with the highest ORs reaching 1.653 (95% CI = 1.233, 2.216; p < 0.01 at rs1012335) in the ACLF-HBV group, and 1.659 (95% CI = 1.274, 2.159; p < 0.01 at rs1012335) in the HCC group. A strongly linked disequilibrium was also found within these two alleles (p < 0.001). Our research indicates that genetic polymorphisms of IFNAR-1 not only contribute to the determination of clearance or chronicity in the early stages of HBV exposure, but they also persistently influence pathogenesis over the long-term process of chronic HBV infection.
He
Xing-Xing
XX
Institute of Liver Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chang
Ying
Y
Jiang
Hua-Jun
HJ
Tang
Feng
F
Meng
Fan-Ying
FY
Xie
Qiong-Hui
QH
Li
Pei-Yuan
PY
Song
Yu-Hu
YH
Lin
Ju-Sheng
JS
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D019694:Hepatitis B, Chronic / Q000150:complications / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008103:Liver Cirrhosis / Q000453:epidemiology / Q000235:genetics; D017093:Liver Failure / Q000453:epidemiology / Q000235:genetics; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053633:Receptor, Interferon alpha-beta / Q000235:genetics* / Q000276:immunology
C507964:IFNAR1 protein, human; D053633:Receptor, Interferon alpha-beta