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Interferon gamma polymorphisms and hepatitis B virus-related liver cirrhosis risk in a Chinese population.

ABSTRACT: BACKGROUND:Previous studies proved that interferon gamma (IFN-?) gene polymorphisms were associated with the risk of hepatitis B virus (HBV) infection. However, the association between IFN-? polymorphisms and HBV-related liver cirrhosis (HBV-LC) risk is still unclear. METHODS:IFN-? +874 T/A and +2109G/A genotypes were determined in 126 HBV-LC patients, 129 chronic hepatitis B(CHB) patients, and 173 early HBV infection controls using a sequence-specific primer-polymerase chain reaction and a polymerase chain reaction-restriction fragment length polymorphism, respectively. RESULTS:Significant associations were observed between +2109A/G polymorphisms and HBV-LC risk in the co-dominant model (GG vs. AA: OR?=?0.321, 95% CI?=?0.130-0.793, P?=?0.014), the allelic model (OR?=?0.565, 95% CI?=?0.388-0.825, P?=?0.003), the dominant model (OR?=?0.551, 95% CI?=?0.344-0.883, P?=?0.013), and the recessive model (OR?=?0.385, 95% CI?=?0.159-0.930, P?=?0.034). In addition, haplotype analysis indicated that the T(+874)G(+2109) haplotype significantly decreased the HBV-LC risk (OR?=?0.106, 95% CI?=?0.022-0.502, P?=?0.000), and A(+874)A(+2109) haplotype significantly increased the LC risk (OR?=?1.485, 95% CI?=?1.065-2.070, P?=?0.019). No significant associations were observed between IFN-? +874 T/A polymorphisms and HBV-LC risk, as well as the two single-nucleotide polymorphisms (SNPs) and CHB risk (P?>?0.05). CONCLUSIONS:Our observations suggested a significant association of IFN-? polymorphisms with HBV-LC risk in the Chinese population.

SUBMITTER: Sun Y

PROVIDER: S-EPMC4389711 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Interferon gamma polymorphisms and hepatitis B virus-related liver cirrhosis risk in a Chinese population.

Sun Yifan Y Lu Yu Y Xie Li L Deng Yan Y Li Shan S Qin Xue X

Cancer cell international 20150331

<h4>Background</h4>Previous studies proved that interferon gamma (IFN-γ) gene polymorphisms were associated with the risk of hepatitis B virus (HBV) infection. However, the association between IFN-γ polymorphisms and HBV-related liver cirrhosis (HBV-LC) risk is still unclear.<h4>Methods</h4>IFN-γ +874 T/A and +2109G/A genotypes were determined in 126 HBV-LC patients, 129 chronic hepatitis B(CHB) patients, and 173 early HBV infection controls using a sequence-specific primer-polymerase chain reac ...[more]

PMID: 25861244

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Project description:Reactive oxygen species (ROS) play critical roles in hepatocarcinogenesis. The catalase (CAT) enzyme is involved in the repair of ROS. Therefore, we investigate the association between CAT gene polymorphisms and the risk of hepatocellular carcinoma (HCC). A total of 715 subjects were divided into 4 groups: 111 chronic hepatitis B (CHB) patients, 90 hepatitis B virus (HBV)-related liver cirrhosis (LC) patients, 266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs1001179, rs769217, and rs7943316 polymorphisms. Binary logistic regression analyses adjusting for sex, age, ethnicity, smoking and alcohol consumption, and body mass index suggested that subjects carrying the rs769217 T allele were at marginally increased risk of CHB, LC, and HCC, with adjusted odds ratios (ORs) of 1.51 (95% confidence interval [CI] = 1.04-2.20, P = 0.029), 1.48 (95% CI = 1.03-2.14, P = 0.035), and 1.51 (95% CI = 1.14-1.98, P = 0.004), respectively. Similarly, those individuals carrying the rs769217 TT genotype had a moderately increased risk of CHB, LC, and HCC, with adjusted ORs of 2.11 (95% CI = 1.05-4.22, P = 0.035), 2.00 (95% CI, 1.01-3.95, P = 0.047), and 1.93 (95% CI = 1.14-3.28, P = 0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least 1 copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HCC, respectively (OR = 1.78, 95% CI = 1.16-2.73, P = 0.009 and OR = 1.83, 95% CI = 1.23-2.71, P = 0.003). This association between CAT rs769217 T alleles and HCC risk is significantly strengthened among men, nonsmokers, nondrinkers, and among individuals <50 years of age. Furthermore, we found 1 high-risk haplotype GTA for CHB (OR = 1.45, 95% CI = 1.05-2.01) and 1 protective haplotype GCA for HCC risk (OR = 0.67, 95% CI = 0.52-0.87). We did not found any significant difference in CAT rs1001179 and rs7943316 polymorphisms between controls and cases. Our findings suggest that the CAT rs769217 T allele is associated with increased risk of CHB, HBV-LC, and HBV-HCC in Guangxi population.

Project description:AimTo evaluate the clinical outcomes of 240-wk treatment with entecavir (0.5 mg) in Chinese nucleoside-naive patients with cirrhosis.MethodsA total of 204 nucleoside-naive patients with compensated (n = 96) or decompensated (n = 108) hepatitis B virus (HBV)-induced cirrhosis at the Department of Gastroenterology of the China-Japan Union Hospital (Jilin University, Changchun, China) who were treated with entecavir (0.5 mg) for 240 wk were enrolled in this study. Liver biopsy samples obtained from 38 patients prior to treatment (baseline) and at week 240 were evaluated by different independent histopathologists. Efficacy assessments included the proportions of patients who achieved an HBV DNA level < 500 copies/mL, the association of interleukin-28B genetic variation with antivirus therapy, clinical outcomes, and histologic improvement. Changes in liver disease severity were analyzed, and liver histologic evaluation was performed in 38 patients with paired biopsies. Student t tests were used to compare the means of continuous variables between the groups, and the proportions of patients who achieved the endpoints were compared using the χ(2) test.ResultsAt week 240, 87.5% of the patients with compensated cirrhosis and 92.6% of the patients with decompensated cirrhosis achieved a HBV DNA level < 500 copies/mL. Three patients had genotypic entecavir resistance within the 240-wk period. No significant association was observed between virologic response and interleukin-28 genotype (CT, 88.2% vs CC, 90.6%). The proportion of patients with Child-Pugh class A disease was significantly increased at week 240 (68%) from the baseline (47%; P < 0.01). The proportion of patients with Child-Pugh class B disease was significantly decreased at week 240 (25%) from the baseline (39%; P = 0.02). In the patients with paired liver biopsies, the mean reduction in the Knodell necroinflammatory score from the baseline was 3.58 ± 1.03 points (7.11 ± 1.80 vs 3.53 ± 1.35, P < 0.01). The mean reduction in Ishak fibrosis score from the baseline was 1.26 ± 0.64 points (5.58 ± 0.50 vs 4.32 ± 0.81, P < 0.01).ConclusionEntecavir is an effective treatment option for patients with HBV-related compensated or decompensated cirrhosis that can result in sustained virologic suppression and histologic improvement.

Dataset Information

Interferon gamma polymorphisms and hepatitis B virus-related liver cirrhosis risk in a Chinese population.

Publications

Interferon gamma polymorphisms and hepatitis B virus-related liver cirrhosis risk in a Chinese population.

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