Virology Unit, Viral Hepatitis Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.
Faculté des Sciences d'El Jadida, Université Chouaib Doukkali, El Jadida, Morocco.
Liver Int. 2018 Mar;38(3):432-442. doi: 10.1111/liv.13533. Epub 2017 Aug 24.
BACKGROUND & AIMS: The natural outcomes of hepatitis C virus (HCV) as well as the progression of the liver disease are highly variable and depend primarily on an efficient immune response. As toll-like receptors seven (TLR7) and eight (TLR8) are important effectors of the innate immunity, this study aims to evaluate the association between TLR7 and TLR8 polymorphisms and the HCV infection outcomes in Moroccan subjects.
In this case-control study, 643 subjects including 293 mild chronic hepatitis patients, 119 with advanced liver disease (AdLD), 93 with HCV spontaneous clearance and 138 healthy controls were genotyped using TaqMan SNPs assays.
Patients carrying TLR7 rs179008-A allele were more likely to clear the virus spontaneously (P = .0001 for women, and P < .001 for men). Besides, carriage of TLR7 rs179009-A allele was associated with a twofold increase in spontaneous viral clearance in female patients (P = .0002), but not in men. In addition, we observed that TLR7 rs179008-T and rs179009-G alleles increased the risk of disease progression in both sexes (P < .05). TLR8 rs3764880-G allele was associated with spontaneous HCV clearance in both sexes (P < .0001) albeit with an apparently stronger association in males (OR = 6.02 for men vs 2.2 for women). In males, TLR8 rs3764879-C and TLR8 rs3764880-A alleles were significantly associated with AdLD status (P < .05).
Our results suggest that variations in TLR7 and TLR8 genes modulate the clearance and progression of HCV infection with different magnitudes between sexes. Our results refine, therefore, our understanding of the sex-specific differences observed regarding the susceptibility to chronic hepatitis.
丙型肝炎病毒（HCV）的自然结局以及肝脏疾病的进展具有高度可变性，主要取决于有效的免疫反应。由于 Toll 样受体 7（TLR7）和 8（TLR8）是先天免疫的重要效应器，本研究旨在评估 TLR7 和 TLR8 多态性与摩洛哥人群 HCV 感染结局之间的关系。
在这项病例对照研究中，我们使用 TaqMan SNP 检测对 643 名研究对象（包括 293 名慢性轻度肝炎患者、119 名进展性肝病患者、93 名 HCV 自发清除患者和 138 名健康对照者）进行了基因分型。
携带 TLR7 rs179008-A 等位基因的患者更有可能自发清除病毒（女性患者 P=0.0001，男性患者 P<0.001）。此外，TLR7 rs179009-A 等位基因与女性患者自发病毒清除率增加两倍相关（P=0.0002），但在男性患者中没有相关性。此外，我们观察到 TLR7 rs179008-T 和 rs179009-G 等位基因增加了两性疾病进展的风险（P<0.05）。TLR8 rs3764880-G 等位基因与两性的 HCV 自发清除相关（P<0.0001），尽管在男性中相关性更强（男性 OR=6.02，女性 OR=2.2）。在男性中，TLR8 rs3764879-C 和 TLR8 rs3764880-A 等位基因与进展性肝病（AdLD）显著相关（P<0.05）。
我们的结果表明，TLR7 和 TLR8 基因的变异以性别间不同的程度调节 HCV 感染的清除和进展。因此，我们的研究结果进一步阐明了两性对慢性肝炎易感性存在差异的原因。
