Dataset Information

Interaction effects among IFN-?+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study.

ABSTRACT: BACKGROUND:The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood. OBJECTIVES:To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes. METHODS:277 individuals infected with HBV and/or HCV, including 81 patients with chronic hepatitis B and C, 122 asymptomatic HBV and/or HCV carriers and 74 controls who cleared HBV and HCV spontaneously, were involved in this study. The SNPs of four genes (rs2069762/-330?G/T of IL-2, rs2430561/+874A>T of IFN-?, rs1800896/-1082G>A?and rs1800872/-592C>A of IL-10 and rs2243250/-589C>T of IL-4) were analysed using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR. The gene-gene interactions were assessed using the multifactor-dimensionality reduction method. RESULTS:Interleukin (IL)-10-592 AC and IL-4-589 CC/CT showed a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-?+874 ?AA and IL-2-330 TT had a synergistic impact (p<0.05). IFN-?+874 ?AA and IL-10-1082 AA had an antagonistic effect (p<0.01) on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis. IL-2-330 TT and IL-10-1082 AA synergistically influenced the clinical outcome (p<0.05). IFN-?+874?AA, IL-2-330 TT and IL-10-1082 AA interactively affected the clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis (p<0.05). CONCLUSIONS:Interactions among polymorphisms of IFN-?+874?AA, IL-2-330 TT, IL-10-1082 AA, IL10--592 AC and IL-4-589 CC/CT significantly influenced the clinical progression of the subjects with HBV and/or HCV infection.

SUBMITTER: Gao QJ

PROVIDER: S-EPMC5577879 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study.

Gao Qiu-Ju QJ Xie Jia-Xin JX Wang Li-Min LM Zhou Qiang Q Zhang Shi-Yong SY

BMJ open 20170823 8

<h4>Background</h4>The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood.<h4>Objectives</h4>To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes.<h4>Metho ...[more]

PMID: 28838891

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Project description:BackgroundThe carcinogenesis of hepatocellular carcinoma is complicated, and genetic factor may have the role in the malignant transformation of liver cells. IL-10 gene polymorphisms have been investigated for their potential roles in hepatocellular carcinoma This study aimed to investigate the relationship between polymorphisms of IL-10 (-1082 A/G, -819 T/C, -592 A/C), and hepatocellular carcinoma by performing a meta-analysis with eligible individual studies.MethodsThis study followed the PRISMA 2020 Checklist. Relevant studies were searched in health-related databases. The Newcastle-Ottawa Scale criteria were used to evaluate the studies quality. Pooled odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and hepatocellular carcinoma using five genetic models. Stratification was done by ethnic groups. Trial sequential analysis (TSA) was performed to determine the required information size.ResultsFifteen case-control studies (n = 8182) were identified. Overall, the heterozygous model showed a marginal significant association only between IL-10 (-1082 A/G) and hepatocellular carcinoma risk (OR: 0.82, 95% CI: 0.67-1.00, 9 studies). On stratification, IL-10 (-1082 A/G) was significantly associated with hepatocellular carcinoma risk in the non-Asian population under dominant (OR: 0.62, 95% CI: 0.45-0.86, 4 studies), heterozygous (OR: 0.60, 95% CI: 0.43-0.85) and allelic models (OR: 0.79, 95% CI: 0.64-0.99). IL-10 (-819 T/C) was significantly associated with hepatocellular carcinoma risk only among non-Asians under the dominant (OR: 1.47, 95% CI: 1.02-2.13, 8 studies), recessive (OR: 1.99, 95% CI: 1.03-3.86, and homozygous models (OR: 2.18, 95% CI: 1.13-4.23). For IL-10 (-592 A/C) with 11 studies, there was no significant association with hepatocellular carcinoma in all five genetic models (P values > 0.5). TSA plots indicated that the information size for firm evidence of effect was sufficient only for the analysis of IL-10 (-592 A/C), but not for the - 1082 A/G or -819 T/C.ConclusionsFindings suggest that IL-10 (-1082 A/G and - 819 T/C) polymorphisms are associated with hepatocellular carcinoma in ethnic-specific manner. However, this evidence is not conclusive because the sample size was insufficient. IL-10 (-592 A/C) polymorphism was not associated with hepatocellular carcinoma albeit with sufficient information size. Future well-designed large case-control studies on IL-10 (-1082 A/G and - 819 T/C) with different ethnicities are recommended.

Project description:BackgroundInterleukin (IL)-6 and IL-10 are the most important cytokine with pro and anti-inflammatory activities, respectively. Dysregulation of IL-6 and IL-10 are associated with increased risk of developing Type 2 Diabetes Mellitus (T2DM). Despite this, a fundamental understanding of both cytokine gene polymorphisms with its expression is critical in understanding of cellular mechanism of insulin resistance as well as T2DM intervention. Therefore, this study aimed to assess IL-6 (- 174 G/C) and IL-10 (- 1082 A/G) gene polymorphism, and its association with T2DM, North West Ethiopia.MethodsA comparative cross-sectional study from January to May 2018 was conducted on study participants with T2DM and apparently healthy controls. Deoxyribonucleic acid (DNA) extraction and genotyping was carried out by using amplification refractory mutation system polymerase chain reaction to detect polymorphism of IL-6 and IL-10 gene at the position - 174 and - 1082, respectively. The logistic regression model was fitted to assess the association of between cytokine gene polymorphisms and T2DM. Odds ratio with 95% CI was determined to assess the presence and strength of association between the explanatory variables and outcome variable. A P-value < 0.05 was considered as statistically significant.ResultParticipants carrying the GG genotype of IL-6 (- 174) (OR (95% CI) = 4.61 (2.07-10.54) was a high likelihood of having T2DM compared to those carrying the CC and AA genotypes. AA and AG genotypes of IL-10 (- 1082) were at lower odd of developing T2DM compared to those carrying the GG genotype. In addition, individuals carrying the G allele of IL-6 (- 174) have 2.82-fold odds of developing T2DM compared to individuals carrying the C allele (OR (95% CI) =2.81 (1.78-4.50)).ConclusionOur study revealed that genetic polymorphisms of IL-6 (- 174) GG genotype is the potential host genetic risk factors to T2DM. While, IL-10 (- 1082) AA genotype is negatively associated with T2DM. Therefore, IL-6 (- 174) and IL-10 (- 1082) genetic variation may be considered as a biomarker for early screening and diagnosis of T2DM.

Dataset Information

Interaction effects among IFN-?+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study.

Publications

Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study.

Similar Datasets

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