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Interferon gamma gene polymorphisms and chronic hepatitis B infections in an Iranian population.

ABSTRACT: BACKGROUND AND AIMS:Chronic hepatitis B is an important health problem in all countries. I Interferon gamma is a pro-inflammatory Th1 cytokines, which can exert antiproliferative and antitumor activity. Some SNPs in IFN-? and IFN-?R1 genes may influence the susceptibility to HBV. Here, we evaluated the impact of interferon gamma (+874 T/A) and its receptor (-611A/G, +189G/C and +95C/T) polymorphisms and the risk of HBV in Iranian patients. MATERIALS AND METHODS:SNPs of interferon gamma and its receptor genotypes were determined in 221 infected patients with HBV and 200 people without HBV using ARMS-PCR and PCR- RFLP method. RESULTS:In this study, we showed an obvious relationship between IFN-? SNPs and susceptibility to chronic HBV. Our findings suggest that IFN-?-874A allele increases the risk of disease and carriers of the T allele have reduced susceptibility to infection. In addition, there was not any relationship between the -611A/G, +189G/C and +95C/T regions of IFN-? R1 and HBV. CONCLUSIONS:Our observations demonstrate +874 T/A SNP as a predicting factor in patients who have the risk of HBV.

SUBMITTER: Heidari Z

PROVIDER: S-EPMC7480198 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Interferon gamma gene polymorphisms and chronic hepatitis B infections in an Iranian population.

Heidari Zahra Z Moudi Bita B Mahmoudzadeh-Sagheb Hamidreza H

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 20200701 7

<h4>Background and aims</h4>Chronic hepatitis B is an important health problem in all countries. I Interferon gamma is a pro-inflammatory Th1 cytokines, which can exert antiproliferative and antitumor activity. Some SNPs in IFN-γ and IFN-γR1 genes may influence the susceptibility to HBV. Here, we evaluated the impact of interferon gamma (+874 T/A) and its receptor (-611A/G, +189G/C and +95C/T) polymorphisms and the risk of HBV in Iranian patients.<h4>Materials and methods</h4>SNPs of interferon ...[more]

PMID: 32897225

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Project description:AIM:To evaluate the efficacy of pegylated interferon in Iranian chronic hepatitis C patients in relation to interferon-? (IFNL) polymorphisms. METHODS:This study enrolled patients with chronic hepatitis C referred to the Tehran Blood Transfusion Hepatitis Clinic in 2011. Patients were included in the study if they had no concomitant hepatic illness, were negative for human immunodeficiency virus antibodies, and had no prior history of treatment with any type of pegylated interferon. Patients were treated with 180 ?g pegylated interferon alpha-2a (Pegaferon(®)) weekly and 800-1200 mg ribavirin daily for 24 or 48 wk depending on weight and hepatitis C virus (HCV) genotype. Blood samples were collected from patients to obtain DNA for determination of IFNL rs12979860 and rs8099917 polymorphisms. The virologic response in patients was then evaluated and compared between the different IFNL genotypes. RESULTS:A total of 152 patients with a mean age of 41.9 ± 10.0 years were included in the study, of which 141/152 were men (92.8%). The most frequent HCV genotype was type-1, infecting 93/152 (61.2%) patients. Sustained virologic response (SVR) was achieved in 81.9% of patients with HCV genotype-1 and 91.1% of patients with HCV genotype-3. Treatment success was achieved in 91.2% (52/57) of patients with the IFNL rs12979860 CC genotype and 82.1% (78/95) in those with other genotypes. Similar treatment response rates were also observed in patients with rs8099917 TT (39/45; 86.7%) and non-TT (61/68; 89.7%) genotypes. Univariate analyses identified the following factors which influenced treatment response for inclusion in a multivariate analysis: age, HCV RNA level, stage of liver fibrosis, rs12979860 CC genotype, and aspartate transaminase level. A logistic regression analysis revealed that only the rs12979860 CC genotype was significantly associated with achievement of SVR (OR = 6.2; 95%CI: 1.2-31.9; P = 0.03). CONCLUSION:The rs12979860 CC genotype was associated with SVR in patients receiving pegylated interferon plus ribavirin, however, the SVR rate in other rs12979860 genotypes was also relatively high.

Project description:BACKGROUND:IL28B gene polymorphism is the best baseline predictor of response to interferon alfa-based antiviral therapies in chronic hepatitis C. Recently, a new IFN-L4 polymorphism was identified as first potential functional variant for induction of IL28B expression. Individualization of interferon alfa-based therapies based on a combination of IL28B/IFN-L4 polymorphisms may help to optimize virologic outcome and economic resources. METHODS:Optimization of treatment outcome prediction was assessed by combination of different IL28B and IFN-L4 polymorphisms in patients with chronic HCV genotype 1 (n?=?385), 2/3 (n?=?267), and 4 (n?=?220) infection treated with pegylated interferon alfa (PEG-IFN) and ribavirin with (n?=?79) or without telaprevir. Healthy people from Germany (n?=?283) and Egypt (n?=?96) served as controls. RESULTS:Frequencies of beneficial IL28B rs12979860 C/C genotypes were lower in HCV genotype 1/4 infected patients in comparison to controls (20-35% vs. 46-47%) this was also true for ss469415590 TT/TT (20-35% vs. 45-47%). Single interferon-lambda SNPs (rs12979860, rs8099917, ss469415590) correlated with sustained virologic response (SVR) in genotype 1, 3, and 4 infected patients while no association was observed for genotype 2. Interestingly, in genotype 3 infected patients, best SVR prediction was based on IFN-L4 genotype. Prediction of SVR with high accuracy (71-96%) was possible in genotype 1, 2, 3 and 4 infected patients who received PEG-IFN/ribavirin combination therapy by selection of beneficial IL28B rs12979860 C/C and/or ss469415590 TT/TT genotypes (p<0.001). For triple therapy with first generation protease inhibitors (PIs) (boceprevir, telaprevir) prediction of high SVR (90%) rates was based on the presence of at least one beneficial genotype of the 3 IFN-lambda SNPs. CONCLUSION:IFN-L4 seems to be the best single predictor of SVR in genotype 3 infected patients. For optimized prediction of SVR by treatment with dual combination or first generation PI triple therapies, grouping of interferon-lambda haplotypes may be helpful with positive predictive values of 71-96%.

Dataset Information

Interferon gamma gene polymorphisms and chronic hepatitis B infections in an Iranian population.

Publications

Interferon gamma gene polymorphisms and chronic hepatitis B infections in an Iranian population.

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