Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients

• Published in: Hepatology international 2011-06, Vol.5 (2), p.681-687
• Main Authors: Bouzgarrou, Nadia, Hassen, Elham, Bahri, Olfa, Gabbouj, Sallouha, Mami, Nabil Ben, Triki, Henda, Chouchane, Lotfi
• Format: Article
• Language: English
• Subjects: Colorectal Surgery; Hepatitis C virus; Hepatology; Medicine; Medicine & Public Health; Original; Original Article; Surgery
• ISSN: 1936-0533; 1936-0541
• DOI: 10.1007/s12072-010-9232-0

Purpose 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. Aim 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). Conclusion 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.