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Relationship between interleukin 18 polymorphisms and susceptibility to chronic hepatitis B virus infection.

ABSTRACT: AIM:To identify the relationship between the tagging single nucleotide polymorphism sites (tagSNPs) of the Interleukin-18 (IL-18) gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese patients. METHODS:Five hundred and one cases of chronic hepatitis B virus (HBV) infection and 301 HBV natural clearance controls were studied. Two tagSNPs in the IL-18 gene (rs1946518A/C and rs574424C/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed. RESULTS:In the genotypes of rs1946518, the AA type was present at a higher frequency in the patients compared to those in the controls. Odds ratio (OR) of the AA genotype for the comparison with that of the AC and the CC genotype was 1.537 (95% confidence intervals (CI): 1.116-2.218, P = 0.009 < 0.025). In phenotypes, the allele C at rs1946518 was of a significantly lower frequency in the patients with chronic hepatitis B than that in the controls (P = 0.017 < 0.025). OR of the allele A for the comparison with that of the allele C was 1.279 (95% CI: 1.045-1.567). As for the rs574424 genotypes, no significant difference in this genotype distribution or in this allele frequency between the patients and the control subjects was observed. No significant difference in the haplotype frequencies between the patients with chronic hepatitis B and HBV natural clearance individuals was displayed. CONCLUSION:The data suggest that genotype AA and the allele A of the IL-18 at position rs1946518 are closely associated with the resistance to chronic hepatitis B and may be the dangerous gene. However, no statistical association was found between polymorphisms of rs574424 for IL-18 and hepatitis B.

SUBMITTER: Li N

PROVIDER: S-EPMC3321489 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Relationship between interleukin 18 polymorphisms and susceptibility to chronic hepatitis B virus infection.

Li Na N Gao Yu-Feng YF Zhang Tian-Chen TC Chen Ping P Li Xu X Su Fei F

World journal of hepatology 20120301 3

<h4>Aim</h4>To identify the relationship between the tagging single nucleotide polymorphism sites (tagSNPs) of the Interleukin-18 (IL-18) gene and genetic susceptibility to chronic hepatitis B virus infection in Chinese patients.<h4>Methods</h4>Five hundred and one cases of chronic hepatitis B virus (HBV) infection and 301 HBV natural clearance controls were studied. Two tagSNPs in the IL-18 gene (rs1946518A/C and rs574424C/G) were genotyped by the Multiplex Snapshot technique. The genotype and ...[more]

PMID: 22489263

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Project description:BACKGROUND:Cytokines are proteins that mediate innate and adaptive immunity responses. It is hypothesized that interferon lambda 3 (IFNL3) levels can influence the outcome of chronic hepatitis B virus (HBV) infection. Polymorphisms in IFN genes have been associated with response to infection. OBJECTIVES:This study was carried-out to investigate the association of IFNL3 gene polymorphisms (rs12979860 and rs8099917) with HBV susceptibility, in chronic HBV-infected patients. PATIENTS AND METHODS:In this case-control study, we determined IFNL3 single nucleotide polymorphisms (SNPs) (rs12979860 and rs8099917) in 221 individuals, with chronic HBV infection, and 200 healthy individuals, who were voluntary blood donors, with negative test for HBV. Alleles and genotypes analyses were performed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS:The frequencies of the rs12979860 and rs8099917 genotypes were not significantly different between the HBV-infected and the control groups (CC:CT:TT of 30.3%:48.0%:21.7% vs. 33.0%:49.0%:18.0%, P > 0.05, and GG:GT:TT of 5.8%:39.4%:54.8% vs. 5.0%:41.0%:54.0%, P > 0.05, respectively). Also, the frequencies of the alleles were not significantly different between both groups (C:T of 54.3%:45.7% vs. 57.5%:42.5%, P > 0.05, and G:T of 25.6%:74.4% vs. 25.5%:74.5%, P > 0.05, respectively) and the chronic HBV infection. There were no significant differences between patients, with at least one rs12979860C and or rs8099917T alleles compared to the healthy controls (rs12979860: CT + CC:TT, OR = 1.26, 95%CI = 0.78 - 2.04, P = 0.341 and rs8099917: GT + TT:GG, OR = 1.03, 95%CI = 0.70 - 1.51, P = 0.877, respectively). CONCLUSIONS:Our study showed no correlation between rs12979860 and rs8099917 SNPs and chronic HBV infection. Further studies, with larger sample sizes and different ethnicities, are necessary to validate our findings.

Project description:BackgroundThe interleukin (IL)18 rs360719 CC genotype is associated with the development of antibodies to hepatitis B virus surface antigen (anti-HBs) in hemodialysis (HD) patients. IL18 shares biological properties with IL12 in promoting the T-hepler 1 (Th1) system. We studied whether polymorphisms in the IL12A 3` untranslated region (UTR) and IL12B 3`UTR may contribute to anti-HBs development (titre ≥ 10 IU/L) in HD patients either individually or jointly with the IL18 polymorphism.MethodsIn 518 HD patients and 240 controls the IL12A rs568408 3'UTR G > A polymorphism was genotyped by high-resolution melting curve analysis. Polymerase chain reaction restriction fragment length polymorphism was used to detect the IL12B rs3212227 3'UTR A > C and IL18 -1297 T > C rs360719 polymorphisms. The associations between the IL12A, IL12B and IL18 genotypes and the risk of impaired anti-HBs development were estimated by computing the odds ratios and their 95% confidence intervals using logistic regression analysis.ResultsIn the logistic regression analysis, the higher frequency of rs360719 CC individually (2.9% in 207 patients without anti-HBs development vs 8.0% in 311 patients with anti-HBs development, p = 0.009) and of rs360719 CC combined with rs568408 GG (p = 0.048), rs568408 GA (p = 0.035), rs568408 GG/AA (p = 0.034) or rs3212227 AA (p = 0.046) was associated with an increased chance for the development of anti-HBs in HD patients. Patients bearing both rs568408 AA and rs360719 TT had a 10.9-fold or 8.9-fold lower chance, respectively, to develop anti-HBs compared with those carrying any other genotype (p = 0.005) or those who had both wild-type rs568408 GG and rs360719 TT (p = 0.011). Carriers of both rs3212227 CC and rs360719 TC had a 4.6-fold lower chance for anti-HBs development than carriers of any other genotype (p = 0.042).ConclusionDevelopment of anti-HBs in HD patients is associated with gene polymorphisms of interleukins involved in the Th1 system.

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Relationship between interleukin 18 polymorphisms and susceptibility to chronic hepatitis B virus infection.

Publications

Relationship between interleukin 18 polymorphisms and susceptibility to chronic hepatitis B virus infection.

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