Ksiaa Cheikhrouhou L, Lakhoua-Gorgi Y, Sfar I, Jendoubi-Ayed S, Aouadi H, Makhlouf M, Ayed K, Ben Abdallah T. Natural evolution of hepatitis C virus infection in hemodialysis Tunisian patients and CTLA-4 SNP's. World J Gastroenterol 2015; 21(35): 10150-10158 [PMID: 26401079 DOI: 10.3748/wjg.v21.i35.10150]
Corresponding Author of This Article
Leila Ksiaa Cheikhrouhou, PhD, Laboratory of Immunology, Charles Nicolle Hospital, Boulevard 9 Avril, Tunis 1006, Tunisia. ksiaaleila@yahoo.fr
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Case Control Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Leila Ksiaa Cheikhrouhou, Yousr Lakhoua-Gorgi, Imen Sfar, Salwa Jendoubi-Ayed, Houda Aouadi, Mouna Makhlouf, Khaled Ayed, Taieb Ben Abdallah, Immunology Research Laboratory of Kidney Transplantation and Immunopathology, Laboratoire de Recherche, LR03SP01, Tunis 1006, Tunisia
Leila Ksiaa Cheikhrouhou, Laboratory of Immunology, Charles Nicolle Hospital, Tunis 1006, Tunisia
Author contributions: Ksiaa Cheikhrouhou L performed the majority of experiments and wrote the manuscript; Lakhoua-Gorgi Y designed the study and corrected the manuscript; Sfar I was involved in the analytical procedures; Jendoubi-Ayed S, Aouadi H and Makhlouf M participated in the collection of the human material; Ayed K served as scientific advisor and participated in the collection of human material; Ben Abdallah T was the guarantor.
Supported by Grant from the Tunisian Kidney Transplantation Research Laboratory (LR03SP01) Fund.
Institutional review board statement: The study was approved by the ethics committee of Charles Nicolle Hospital (Tunis, Tunisia).
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at ksiaaleila@yahoo.fr.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Leila Ksiaa Cheikhrouhou, PhD, Laboratory of Immunology, Charles Nicolle Hospital, Boulevard 9 Avril, Tunis 1006, Tunisia. ksiaaleila@yahoo.fr
Telephone: +216-98427899 Fax: +216-71561156
Received: January 26, 2015 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 Processing time: 234 Days and 16.1 Hours
Abstract
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.
