<abstract xmlns="http://www.w3.org/1999/xhtml">Hepatitis C virus (HCV) infection represents a serious health problem. The –174 G/C mutation in the pro inflammatory cytokine interleukin-6 (IL-6) is associated with developing liver diseases. Likewise, the S and Z mutations in the serine protease inhibitor α1-antitrypsin (A1AT) are associated with pulmonary emphysema and/or liver cirrhosis. We explored the distribution of the single nucleotide polymorphisms (SNPs) of <italic>IL-6</italic> and <italic>A1AT</italic> genes in chronic HCV-infected patients and evaluated their impact on the progression of liver cirrhosis.One hundred and fifty Egyptian HCV-infected patients together with 100 healthy controls were enrolled in this study. The patient groups were subdivided into chronic hepatitis patients (<italic>n</italic> = 85) and cirrhotic patients (<italic>n</italic> = 65). The SNP of IL-6 (–174 G/C, rs1800795), A1AT Z mutation (342 Glu/Lys, rs28929474) and A1AT S mutation (264 Glu/Val, rs17580) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Cirrhotic patients exhibited significantly increased frequency of the A1AT S allele compared with the controls (34.6 <italic>vs</italic>. 5.0%), while the chronic hepatitis patients showed a higher frequency of the A1AT Z allele compared with the controls (14.7 <italic>vs</italic>. 2.5%). Remarkably, IL-6 (CC genotype) was detected only in the chronic hepatitis patients. Multivariate regression analysis showed that aspartate transaminase (AST) and the S alleles of A1AT, represented as SS+MS genotypes, were significantly independent predictors for development of liver cirrhosis. We concluded that inheritance of deficient S and Z alleles of the <italic>A1AT</italic> gene but not IL-6 (–174 G/C), were associated with progressive liver diseases.</abstract>

Hepatitis C virus (HCV) infection represents a serious health problem. The –174 G/C mutation in the pro inflammatory cytokine interleukin-6 (IL-6) is associated with developing liver diseases. Likewise, the S and Z mutations in the serine protease inhibitor α1-antitrypsin (A1AT) are associated with pulmonary emphysema and/or liver cirrhosis. We explored the distribution of the single nucleotide polymorphisms (SNPs) of IL-6 and A1AT genes in chronic HCV-infected patients and evaluated their impact on the progression of liver cirrhosis.One hundred and fifty Egyptian HCV-infected patients together with 100 healthy controls were enrolled in this study. The patient groups were subdivided into chronic hepatitis patients (n = 85) and cirrhotic patients (n = 65). The SNP of IL-6 (–174 G/C, rs1800795), A1AT Z mutation (342 Glu/Lys, rs28929474) and A1AT S mutation (264 Glu/Val, rs17580) were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Cirrhotic patients exhibited significantly increased frequency of the A1AT S allele compared with the controls (34.6 vs. 5.0%), while the chronic hepatitis patients showed a higher frequency of the A1AT Z allele compared with the controls (14.7 vs. 2.5%). Remarkably, IL-6 (CC genotype) was detected only in the chronic hepatitis patients. Multivariate regression analysis showed that aspartate transaminase (AST) and the S alleles of A1AT, represented as SS+MS genotypes, were significantly independent predictors for development of liver cirrhosis. We concluded that inheritance of deficient S and Z alleles of the A1AT gene but not IL-6 (–174 G/C), were associated with progressive liver diseases.

Polymorphisms of α1-antitrypsin and Interleukin-6 genes and the progression of hepatic cirrhosis in patients with a hepatitis C virus infection

Department of Medical Biochemistry and Molecular Biology

Balkan Journal of Medical Genetics

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Hepatitis C virus (HCV) infection represents a serious health problem. The –174 G/C mutation in the pro inflammatory cytokine interleukin-6 (IL-6) is...

Polymorphisms of α1-antitrypsin and Interleukin-6 genes and the progression of hepatic cirrhosis in patients with a hepatitis C virus infection

Article Category: Original Article

Published Online: Dec 31, 2016

Page range: 35 - 44

DOI: https://doi.org/10.1515/bjmg-2016-0034

Keywords
α1 Antitrypsin (A1AT), Cirrhosis, Inter-leukin 6 (IL-6), Hepatitis C virus (HCV) infection, Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Polymorphism

© 2016 Motawi T, Shaker OG, Hussein RM, Houssen M

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Polymorphisms of α1-antitrypsin and Interleukin-6 genes and the progression of hepatic cirrhosis in patients with a hepatitis C virus infection

Article Category: Original Article

Published Online: Dec 31, 2016

Page range: 35 - 44

DOI: https://doi.org/10.1515/bjmg-2016-0034

Keywordsα1 Antitrypsin (A1AT), Cirrhosis, Inter-leukin 6 (IL-6), Hepatitis C virus (HCV) infection, Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Polymorphism

© 2016 Motawi T, Shaker OG, Hussein RM, Houssen M

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords
α1 Antitrypsin (A1AT), Cirrhosis, Inter-leukin 6 (IL-6), Hepatitis C virus (HCV) infection, Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), Polymorphism