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

Nadia Bouzgarrou, Elham Hassen, Olfa Bahri, Sallouha Gabbouj, Nabil Ben Mami, Henda Triki, Lotfi Chouchane

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)681-687
Number of pages7
JournalHepatology International
Volume5
Issue number2
DOIs
Publication statusPublished - Jun 2011

Fingerprint

Liver Cirrhosis
Anti-Inflammatory Agents
Cytokines
Interleukin-18
Genotype
Genes
Interleukin-10
Fibrosis
Interferons
Chronic Hepatitis C
Polymerase Chain Reaction
Hepatitis C
Restriction Fragment Length Polymorphisms
Single Nucleotide Polymorphism
Logistic Models
Alleles
Regression Analysis
Liver

Keywords

  • Cirrhosis
  • Combined analysis
  • Cytokine
  • Hepatitis C
  • Polymorphism

ASJC Scopus subject areas

  • Hepatology

Cite this

Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients. / Bouzgarrou, Nadia; Hassen, Elham; Bahri, Olfa; Gabbouj, Sallouha; Mami, Nabil Ben; Triki, Henda; Chouchane, Lotfi.

In: Hepatology International, Vol. 5, No. 2, 06.2011, p. 681-687.

Research output: Contribution to journalArticle

Bouzgarrou, Nadia ; Hassen, Elham ; Bahri, Olfa ; Gabbouj, Sallouha ; Mami, Nabil Ben ; Triki, Henda ; Chouchane, Lotfi. / Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients. In: Hepatology International. 2011 ; Vol. 5, No. 2. pp. 681-687.
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AU - Hassen, Elham

AU - Bahri, Olfa

AU - Gabbouj, Sallouha

AU - Mami, Nabil Ben

AU - Triki, Henda

AU - Chouchane, Lotfi

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N2 - 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.

AB - 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.

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