title: Association of genetic polymorphisms in CD8+ T cell inhibitory genes and susceptibility to and progression of chronic HBV infection.
abstract: BACKGROUND
  Previous studies have shown that multiple inhibitory genes play an important role in HBV-specific CD8+ T cell exhaustion and dysfunction in the setting of chronic HBV infection. Polymorphic variants of these genes are thought to be predisposing factors for HBV susceptibility, clearance, and disease progression. The aim of this retrospective study was to identify variants affecting chronic HBV infection in a Chinese Han population.
  
  
  METHODS
  We chose 28 tgSNPs from HapMap data on 5 key genes. They were genotyped on a total of 858 chronic HBV patients, 429 patients who underwent spontaneous recovery, and 239 healthy controls. We evaluated the correlation between the polymorphisms and HBV susceptibility, spontaneous clearance, and disease progression.
  
  
  RESULTS
  The association of rs3827537 of BIM genotype TA and allele A was significantly different (P=0.016, OR=2.049; P=0.031, OR=1.925) between HBV patients and healthy controls. The rs36084323 of PD-1, as well as rs3766377, rs485618, rs4656942 of CD244 showed significant associations with the risk for HBV-related cirrhosis and hepatocellular carcinoma (HCC) (P=0.009, OR=0.482; P=0.009, OR=4.573; P=0.015, OR=0.580; P=0.028, OR=2.855). MDR analysis revealed that the four SNPs (rs36084323, rs3766377, rs485618, rs4656942) modulated the predisposition to cirrhosis and HCC in patients with chronic HBV infection (P=0.006). Using a luciferase reporter assay, we demonstrated that various alleles of rs3766377 had differential effects, and rs3766377 and rs485618 might have interactive effects.
  
  
  CONCLUSIONS
  The present study reveals genetic associations among PD-1 and CD244 variants that may be involved in the development of cirrhosis and HCC in patients with chronic HBV infection. The BIM variant was associated with HBV susceptibility.
authors: Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Hong
authors: H
authors: Peng
authors: Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
authors: Qing-Ling
authors: QL
authors: Li
authors: Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Si-Hui
authors: SH
authors: Hou
authors: Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Jun
authors: J
authors: Hu
authors: Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors: Jia-Hao
authors: JH
authors: Fan
authors: Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: guojinjun1972@163.com.
authors: Jin-Jun
authors: JJ
authors: Guo
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006801:Humans; D056747:Immunomodulation / Q000235:genetics*; D008111:Liver Function Tests; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics; D000071176:Signaling Lymphocytic Activation Molecule Family; D019562:Viral Load
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C084093:CD244 protein, human; D008565:Membrane Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011518:Proto-Oncogene Proteins; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family
keywords: Bcl-2 homolog (Bim); CD244 (2B4); Genetic polymorphism; Hepatitis B virus (HBV); Programmed cell death 1 (PD-1)