Toll 样受体 9 多态性与摩洛哥慢性携带者乙型肝炎病毒清除。

Toll-like receptor 9 polymorphisms and Hepatitis B virus clearance in Moroccan chronic carriers.

机构信息

Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco; Laboratoire de Biotechnologie, Biochimie et Nutrition - Université Chouaib Doukkali, Faculté des Sciences d'El Jadida, 24000 El Jadida, Morocco.

Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.

出版信息

Gene. 2019 Mar 1;687:212-218. doi: 10.1016/j.gene.2018.11.041. Epub 2018 Nov 16.

DOI:10.1016/j.gene.2018.11.041

PMID:30453064

Abstract

OBJECTIVES

Toll-like receptor 9 (TLR9) plays a crucial role in the innate immune response against viral infections. The failure of this system may result, in an attenuated immune response against HBV. Recent research has focused on the possibility of targeting the defects in TLR9 pathway as a novel approach for anti-HBV treatment. Our study aimed to assess the impact of both TLR9 rs5743836 and rs187084 polymorphisms on spontaneous HBV clearance in Moroccan chronic HBV carriers.

METHODS

In this study, 239 individuals chronically infected with HBV (CHB) and 133 subjects who spontaneously resolved the infection (SRB) were genotyped using a Taqman allelic discrimination assay.

RESULTS/CONCLUSION: Remarkably, we observed a dosage effect of both SNPs on viral loads; with a significant increase of circulating HBV DNA within AA, AG to GG rs5743836 genotypes, whereas the inverse phenomenon was noticed within rs187084 genotypes. There were no consistent association between TLR9 polymorphisms and spontaneous clearance of HBV, however, a significant association was observed between rs187084 AA genotype and HBV progression to advanced liver disease. Further studies on larger populations might be necessary to understand the modulating effect of TLR9 polymorphisms on HBV loads that remain a viral factor of paramount importance to predict HCC development.

摘要

目的

Toll 样受体 9（TLR9）在抗病毒感染的固有免疫反应中起着至关重要的作用。该系统的失效可能导致针对乙型肝炎病毒（HBV）的免疫应答减弱。最近的研究集中在靶向 TLR9 途径缺陷作为抗 HBV 治疗新方法的可能性上。本研究旨在评估 TLR9 rs5743836 和 rs187084 多态性对摩洛哥慢性 HBV 携带者自发性 HBV 清除的影响。

方法

在这项研究中，使用 Taqman 等位基因鉴别分析对 239 名慢性 HBV 感染（CHB）个体和 133 名自发清除感染（SRB）个体进行了基因分型。

结果/结论：值得注意的是，我们观察到这两个 SNP 对病毒载量都有剂量效应；AA、AG 到 GG rs5743836 基因型的循环 HBV DNA 显著增加，而 rs187084 基因型则出现相反现象。TLR9 多态性与 HBV 自发性清除之间没有一致的关联，但 rs187084 AA 基因型与 HBV 进展为晚期肝病之间存在显著关联。需要对更大的人群进行进一步研究，以了解 TLR9 多态性对 HBV 载量的调节作用，HBV 载量仍然是预测 HCC 发展的一个至关重要的病毒因素。