Association of genetic polymorphisms in CD8+ T cell inhibitory genes and susceptibility to and progression of chronic HBV infection.

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Association of genetic polymorphisms in CD8+ T cell inhibitory genes and susceptibility to and progression of chronic HBV infection.

Infect Genet Evol. 2015 Aug 18;

Authors: Peng H, Li QL, Hou SH, Hu J, Fan JH, Guo JJ

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 tgSNP 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.

PMID: 26296604 [PubMed - as supplied by publisher]