Published online Sep 21, 2015. doi: 10.3748/wjg.v21.i35.10150
Peer-review started: January 27, 2015
First decision: February 10, 2015
Revised: April 1, 2015
Accepted: June 9, 2015
Article in press: June 9, 2015
Published online: September 21, 2015
AIM: To analyze the polymorphisms of CTLA-4 gene involved in the response against hepatitis C virus (HCV) infection.
METHODS: We recruited 500 hemodialysed patients from several hemodialysis centers, all HCV-antibody positive, spread over different regions of Tunisia, as part of a national survey in 2008 conducted in the laboratory of immunology at the Charles Nicolle hospital Tunisia, classified into two groups G1 (PCR+) and G2 (PCR-) according to the presence or absence of viral RNA. Of these patients, 307 were followed prospectively on a viral molecular level over a period from 2002 to 2008, divided into two groups based on the persistence and viral clearance. PCR-RFLP was performed for the analysis of SNPs (+49) A/G and (+6230) G/A CTLA-4 for these 500 patients and 358 healthy controls.
RESULTS: Analysis of clinical and virological characteristics of our cohort suggests a nosocomial infection in our hemodialysed patients with transfusion history as a primary risk factor and a predominance of genotype 1b. The haplotype analysis revealed an increase of frequencies of GG (+49)/(CT60) CTLA-4 in the entire patients group compared to controls (P = 0.0036 and OR = 1.42; 95%CI: 1.12-1.79, respectively). This haplotype is therefore associated with susceptibility to HCV infection.
CONCLUSION: Our study suggests a possible role of CTLA-4 polymorphisms in the outcome of HCV infection in the Tunisian hemodialysed population.
Core tip: Clinical and virological characteristics of our cohort suggest a nosocomial hepatitis C virus (HCV) infection in Tunisian hemodialysis patients with transfusion history as a primary risk factor and a predominance of genotype 1b. No significant association was found for the two CTLA-4 SNPs studied either to spontaneous clearance, persistence or protection against HCV infection. The GG (+49)/(CT60) CTLA-4 haplotype is therefore associated with susceptibility to HCV infection. The study of other susceptibility genes for HCV infection will certainly allow a better understanding of the molecular mechanisms of spontaneous viral clearance or persistence of HCV infection.