title: Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients.
abstract: OBJECTIVE
  Chronic hepatitis C progression is commonly attributed to the continuous activation of the immune response with an increased production of pro-inflammatory cytokines, leading to fibrosis and ultimately to cirrhosis. On the contrary, anti-inflammatory cytokines, mainly interleukin (IL)-10 have a modulatory effect on hepatic fibrogenesis. The association between individual polymorphisms within cytokine genes and hepatitis C outcome is often weak and non-informative. Interestingly, it has been demonstrated that a combination of specific genotypes may be a more significant and powerful approach for predicting disease risk.
  
  
  OBJECTIVE
  This study is aimed at investigating the combined effect of single nucleotide polymorphism (SNP) in IL-18 (-607C/A, -137G/C), interferon (IFN)-γ (+874T/A) and IL-10 (-1082G/A) genes on cirrhosis risk in HCV-infected patients.
  
  
  METHODS
  Seventy-seven chronic hepatitis C Tunisian subjects were included in this study. The patients were divided into two groups: the first included 31 non-cirrhotic patients, and the second included 46 liver cirrhosis patients. IL-18 genotyping was performed using the PCR amplification and the restriction fragment length polymorphism analysis (RFLP). IFN-γ and IL-10 polymorphisms were analyzed using the allele-specific PCR (AS-PCR).
  
  
  RESULTS
  The combined high-risk genotype (IL-18 -607C/*, IL-18 -137G/*, IFN-γ +874T/*, IL-10 -1082A/A) frequency was compared between patients with and those without cirrhosis. Individuals were classified according the number of high-risk genotypes as follows: (0-2), patients with at most two high-risk genotypes; (3-4), patients with at least three of the high-risk genotypes. The logistic regression analysis showed that patients harboring 3-4 putative high-risk genotypes have a fivefold higher risk for developing cirrhosis in comparison to those harboring at most two high-risk genotypes (OR = 5.19; 95% CI = 1.49-18.05; p = 0.009).
  
  
  CONCLUSIONS
  Our study showed that the co-inheritance of IL-18, IFN-γ and IL-10 specific high-risk genotypes is associated with a greater risk for liver cirrhosis.
authors.affiliation: Molecular Immuno-oncology Laboratory, Faculty of Medicine, Monastir, Tunisia, nadia.bouzgarrou@lycos.com.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bouzgarrou
authors.forename: Elham
authors.initials: E
authors.lastname: Hassen
authors.forename: Olfa
authors.initials: O
authors.lastname: Bahri
authors.forename: Sallouha
authors.initials: S
authors.lastname: Gabbouj
authors.forename: Nabil Ben
authors.initials: NB
authors.lastname: Mami
authors.forename: Henda
authors.initials: H
authors.lastname: Triki
authors.forename: Lotfi
authors.initials: L
authors.lastname: Chouchane