The genetic association of cytokine genes, single nucleotide polymorphisms, and the incidence of liver cirrhosis in chronic hepatitis C Egyptian patients

Abstract

Cytokines play a central role in regulating the anti-viral responses against hepatitis C virus (HCV). The objective of this study were to evaluate the effect of proinflammatory cytokines (IL-18 − 607 C/A, rs 1946518; IL-18 − 137 G/C, rs 187283; INF-γ + 874 T/A, rs 240561), SNPs, and the anti-inflammatory cytokine (IL-10 + 1082 G/A, rs 1800896) SNPs on the risk of development of hepatic cirrhosis in Egyptian patients and to evaluate the combined effect of the polymorphic variants that show an interrelation with the risk of hepatic cirrhosis. The study included 63 chronic HCV patients. The patients were stratified into two groups. Group 1 consisted of 33 cirrhotic chronic hepatitis C patients while the second group consisted of 30 non-cirrhotic chronic hepatitis C patients that were taken as a control group. Genotyping of IFN-γ (+ 874 T/A) and IL-10 (− 1082 G/A) SNPs was performed by allele-specific PCR technique (AS-PCR). Genotyping of IL-18 (− 607 C/A) and IL-18 (− 137 G/C) SNPs was determined by PCR-RFLP technique. Analysis of IFN-γ (+ 874 T/A) SNP revealed that the T allele and the TT genotype were significantly higher in cirrhotic patients' group compared to non-cirrhotic group (P < 0.001 and P = 0.004, respectively). Analysis of IL-10 (− 1082 G/A) SNP revealed that the A allele and AA genotype were significantly higher in the cirrhotic patients' group (P = 0.001 and P = 0.047, respectively). Regression analysis revealed that IFN-γ Hi/IL-10 Lo combined genotypes were significantly higher in liver cirrhosis patients compared to non-cirrhotic patients (P = 0.002). INF-γ (+ 874 T/A) and IL-10 (+ 1082 G/A) SNPs might be associated with occurrence of hepatic cirrhosis in chronic HCV Egyptian patients.

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