白细胞介素28B和细胞间黏附分子-1基因多态性对丙型肝炎病毒感染患者直接抗病毒治疗反应的影响

Impact of Interleukin 28B and ICAM-1 Genetic Polymorphisms on Response to Direct Antiviral Treatment Among HCV Infected Patients.

作者信息

Elsheredy Amel G, Almaeen Abdulrahman H, Ghazy Amany A, Helaly Ghada F, Amer Ibrahim, Ghazy Haneen A, Haydara Tamer

机构信息

Department of Microbiology, Medical Research Institute, Alexandria University, Alexandria, Egypt.

Department of Pathology, College of Medicine, Jouf University, Sakaka, Saudi Arabia.

出版信息

Endocr Metab Immune Disord Drug Targets. 2020;20(8):1328-1335. doi: 10.2174/1871530320666200505113619.

DOI:10.2174/1871530320666200505113619

PMID:32368983

Abstract

BACKGROUND

Single nucleotide polymorphisms (SNPs) of IL-28B and/or ICAM-1 could have a role in expecting a response from HCV infected patients to direct antiviral agents (DAAs).

OBJECTIVE

The aim of the current study was to investigate the impact of IL-28B rs12979860 and rs8099917, and, ICAM-1 rs281437 SNPs on response to treatment with sofosbuvir + Daclatsvir ± Ribavirin, among HCV-infected Egyptian patients.

METHODS

Whole blood genomic DNA was extracted from 120 participants (80 HCV-infected patients and 40 healthy volunteers). HCV-infected patients were subdivided into responders and nonresponders to DAAs. Liver function testing, anti-HCV antibodies, HCV-RNA viral load and HCV genotyping were performed. IL-28B and ICAM-1 SNPs were evaluated by real-time PCR.

RESULTS

ALT and AST levels were significantly higher among non-responder HCV infected patients (P = 0.001*). 90% of the patients had HCV genotype 4a and the remaining 10% had 4l genotype. Allelic discrimination revealed that IL-28B rs12979860 T, IL-28B rs809917 T and ICAM-1 rs281437 C alleles were more frequent among HCV-infected patients (responders or non-responders) than controls. However, IL-28B rs8099917 G allele was more frequent among healthy controls. Regarding the response to DAAs treatment, HCV-infected patients with IL-28B rs8099917 GG genotype showed a significantly earlier viral response compared to those carrying TT alleles. ICAM-1 rs281437 CT alleles were non significantly more frequent among responders. However, IL-28B rs12979860 alleles did not show any difference.

CONCLUSION

Genotyping of IL-28B rs8099917 is a useful independent tool for expecting a response of Egyptian HCV-infected patients to DAAs.

摘要

背景

白细胞介素-28B（IL-28B）和/或细胞间黏附分子-1（ICAM-1）的单核苷酸多态性（SNP）可能在预测丙型肝炎病毒（HCV）感染患者对直接抗病毒药物（DAA）的反应中发挥作用。

目的

本研究旨在调查IL-28B rs12979860和rs8099917以及ICAM-1 rs281437单核苷酸多态性对埃及HCV感染患者使用索磷布韦+达卡他韦±利巴韦林治疗反应的影响。

方法

从120名参与者（80名HCV感染患者和40名健康志愿者）中提取全血基因组DNA。将HCV感染患者分为对DAA有反应者和无反应者。进行肝功能测试、抗HCV抗体、HCV-RNA病毒载量和HCV基因分型。通过实时聚合酶链反应评估IL-28B和ICAM-1单核苷酸多态性。

结果

无反应的HCV感染患者的丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平显著更高（P = 0.001*）。90%的患者为HCV基因4a型，其余10%为4l型。等位基因鉴别显示，与对照组相比，IL-28B rs12979860 T、IL-28B rs809917 T和ICAM-1 rs281437 C等位基因在HCV感染患者（有反应者或无反应者）中更为常见。然而，IL-28B rs8099917 G等位基因在健康对照组中更为常见。关于对DAA治疗的反应，与携带TT等位基因的患者相比，IL-28B rs8099917 GG基因型的HCV感染患者显示出明显更早的病毒反应。有反应者中ICAM-1 rs281437 CT等位基因的频率略高，但无统计学意义。然而，IL-28B rs12979860等位基因没有显示出任何差异。