title: Polymorphisms of α1-antitrypsin and Interleukin-6 genes and the progression of hepatic cirrhosis in patients with a hepatitis C virus infection.
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) ofIL-6andA1ATgenes 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 (34.6vs. 5.0%), while the chronic hepatitis patients showed a higher frequency of the A1AT Z allele compared with the controls (14.7vs. 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 theA1ATgene but not IL-6 (-174 G/C), were associated with progressive liver diseases.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: T
authors.initials: T
authors.lastname: Motawi
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.
authors.forename: O G
authors.initials: OG
authors.lastname: Shaker
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: R M
authors.initials: RM
authors.lastname: Hussein
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt.
authors.forename: M
authors.initials: M
authors.lastname: Houssen
keywords: Cirrhosis; Hepatitis C virus (HCV) infection; Inter-leukin 6 (IL-6); Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP); Polymorphism; α1 Antitrypsin (A1AT)