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Abstract
Background and AimCytokine-inducible SRC homology 2 domain protein (CISH) is the first member of the suppressors of cytokine signaling (SOCS) protein family. An association between multiple CISH polymorphisms and susceptibility to infectious diseases has been reported. This study aimed to investigate the possible association of these single nucleotide polymorphisms (SNPs) in CISH gene with different outcomes of Hepatitis B virus (HBV) infection.Methods1019 unrelated Chinese Han subjects, including 240 persistent asymptomatic HBV carriers, 217 chronic hepatitis B patients, 137 HBV-related liver cirrhosis patients, and 425 cases of spontaneously recovered HBV as controls, were studied. Four SNPs (rs622502, rs2239751, rs414171 and rs6768300) in CISH gene were genotyped with the snapshot technique. Transcriptional activity of the CISH promoter was assayed in vitro using the dual-luciferase reporter assay system.ResultsAt position rs414171, A allele and AA genotype frequencies were significantly higher in the HBV-resolved group as compared to the persistent HBV infection group. At position rs2239751, TT genotype was further observed in the HBV-resolved group. Using asymptomatic HBV carriers as controls, our results indicated that the rs414171 and rs2239751 polymorphisms were unrelated to HBV progression. The other two SNPs (rs622502 and rs6768300) showed no association with persistent HBV infection. Haplotype analysis revealed that the GGCA haplotype was associated with spontaneous clearance of HBV in this population. Moreover, luciferase activity was significantly higher in the PGL3-Basic-rs414171T construct as compared to the PGL3-Basic-rs414171A construct (p<0.001).ConclusionTwo SNPs (rs414171 and rs2239751) in the CISH gene were associated with persistent HBV infection in Han Chinese population, but not with HBV progression.
Highlights
Hepatitis B virus (HBV) infection remains a global health problem
Patients with chronic HBV infection are at risk of developing diverse severe outcomes, including liver cirrhosis, liver failure, or hepatocellular carcinoma (HCC) [1]
Recent studies have suggested that Cytokine-inducible SRC homology domain protein (CISH) is involved in human diseases [9,10], and polymorphisms in CISH gene are associated with susceptibility to infectious diseases [11], including bacteremia, malaria, tuberculosis and Hepatitis B [12]
Summary
Hepatitis B virus (HBV) infection remains a global health problem. Patients with chronic HBV infection are at risk of developing diverse severe outcomes, including liver cirrhosis, liver failure, or hepatocellular carcinoma (HCC) [1]. Cytokine-inducible SH2-containing protein (CISH), the first identified member of the SOCS protein family,can be induced in response to stimulation by different cytokines, and negatively regulates the signaling of cytokines, in particular IL-2. Recent studies have suggested that CISH is involved in human diseases [9,10], and polymorphisms in CISH gene are associated with susceptibility to infectious diseases [11], including bacteremia, malaria, tuberculosis and Hepatitis B [12]. We aimed to investigate the possible relationship between these CISH polymorphisms (rs622502, rs2239751, rs414171 and rs6768300) and the different outcomes of HBV infection in Chinese Han population. This study aimed to investigate the possible association of these single nucleotide polymorphisms (SNPs) in CISH gene with different outcomes of Hepatitis B virus (HBV) infection
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