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突尼斯血液透析患者丙型肝炎病毒感染的自然演变及细胞毒性T淋巴细胞相关抗原4单核苷酸多态性

Natural evolution of hepatitis C virus infection in hemodialysis Tunisian patients and CTLA-4 SNP's.

作者信息

Ksiaa Cheikhrouhou Leila, Lakhoua-Gorgi Yousr, Sfar Imen, Jendoubi-Ayed Salwa, Aouadi Houda, Makhlouf Mouna, Ayed Khaled, Ben Abdallah Taieb

机构信息

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.

出版信息

World J Gastroenterol. 2015 Sep 21;21(35):10150-8. doi: 10.3748/wjg.v21.i35.10150.

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.

摘要

目的

分析参与丙型肝炎病毒(HCV)感染应答的细胞毒性T淋巴细胞相关抗原4(CTLA-4)基因的多态性。

方法

作为突尼斯查尔斯·尼科勒医院免疫学实验室2008年开展的一项全国性调查的一部分,我们从突尼斯不同地区的几个血液透析中心招募了500名血液透析患者,他们均为HCV抗体阳性。根据病毒RNA的有无将其分为两组,G1组(PCR阳性)和G2组(PCR阴性)。在这些患者中,307名患者于2002年至2008年期间在病毒分子水平上进行了前瞻性随访,根据病毒持续存在和清除情况分为两组。对这500名患者和358名健康对照进行PCR-RFLP分析,以检测CTLA-4基因的单核苷酸多态性(+49)A/G和(+6230)G/A。

结果

对我们队列的临床和病毒学特征分析表明,有输血史的血液透析患者发生医院感染,输血史是主要危险因素,且以1b基因型为主。单倍型分析显示,与对照组相比,整个患者组中GG(+49)/(CT60)CTLA-4的频率增加(P = 0.0036,OR = 1.42;95%可信区间:分别为1.12 - 1.79)。因此,该单倍型与HCV感染易感性相关。

结论

我们的研究表明,CTLA-4基因多态性在突尼斯血液透析人群HCV感染结局中可能发挥作用。

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