ABSTRACT

Background: Single nucleotide polymorphisms (SNPs) of the interferon lambda 3 (IFN-λ 3) gene are associated with viral clearance and treatment response in chronic hepatitis C virus (HCV) infection.

Aim: to assess whether specific IFN-λ 3 gene SNP, known as rs12979860 (C > T), could predict the outcome of treatment with direct acting antivirals (DAAs) among Egyptian patients with chronic HCV genotype 4 infection.

Methods: Tetra-primer (ARMS-PCR) and PCR-RFLP methods were used for SNP genotyping in 100 chronic HCV-infected patients and 50 healthy subjects as control group.

Results: The CC (wild type) genotype of rs12979860 was identified in 20 patients, 50% of them achieved sustained virological response (SVR). SNP genotype TT was found in 17 patients and only 2 of them (11.76%) were responders. The frequency of CT genotypes was significantly higher in responders than in non-responders (p= .021). In contrast, the frequency of TT genotypes was significantly higher in non-responders (42.85%, p< .001). On univariate and multivariate logistic regression analyses of the significant predictors of SVR, there were six predictive factors (Age, diabetes mellitus, AST, albumin, type of therapy and IFN-λ 3 genotype).

Conclusion: The TT genotype and T allele were significantly associated with failure to achieve SVR. However, CT genotype of IFN-λ 3 (rs12979860) may be considered as a predictor for SVR in patients who received DAAs.

摘要

背景：干扰素 λ 3 (IFN-λ 3) 基因的单核苷酸多态性 (SNP) 与慢性丙型肝炎病毒 (HCV) 感染的病毒清除和治疗反应有关。

目的：评估特定的 IFN-λ 3 基因 SNP（称为 rs12979860 (C > T)）是否可以预测埃及慢性 HCV 基因型 4 感染患者使用直接作用抗病毒药物 (DAA) 的治疗结果。

方法：采用四引物（ARMS-PCR）和PCR-RFLP方法对100名慢性HCV感染患者和50名健康受试者作为对照组进行SNP基因分型。

结果：在20名患者中鉴定出rs12979860的CC（野生型）基因型，其中50%获得了持续病毒学应答（SVR）。在 17 名患者中发现了 SNP 基因型 TT，其中只有 2 名 (11.76%) 是应答者。应答者的 CT 基因型频率明显高于无应答者 ( p = .021)。相比之下，无反应者中 TT 基因型的频率明显更高（42.85%，p < .001）。在 SVR 显着预测因子的单变量和多变量逻辑回归分析中，有六个预测因素（年龄、糖尿病、AST、白蛋白、治疗类型和 IFN-λ 3 基因型）。

结论：TT 基因型和 T 等位基因与未能实现 SVR 显着相关。然而，在接受 DAA 的患者中，IFN-λ 3 (rs12979860) 的 CT 基因型可被视为 SVR 的预测因子。