完整标题：白细胞介素-28B rs12979860基因多态性对摩洛哥慢性丙型肝炎患者治疗反应的影响

The complete title: The effect of interleukin-28B rs12979860 polymorphism on the therapeutic response of Moroccan patients with chronic hepatitis C.

作者信息

Nadia Kandoussi, Hicham Elannaz, Reda Tagajdid Mohamed, Nadia Touil, Elarbi Bouaiti, Saâd Elkabbaj, Mimoun Zouhdi, Saâd Mrani

机构信息

Research Team in Molecular Virology and Oncobiology, Faculty of Medicine and Pharmacy, University Mohammed V, BP 6203 Rabat, Morocco; Research Laboratory and Medical Analysis of the Royal Mounted Police, Av. ibn sina, Agdal, Rabat 10100, Morocco.

Research Team in Molecular Virology and Oncobiology, Faculty of Medicine and Pharmacy, University Mohammed V, BP 6203 Rabat, Morocco; Laboratory of Virology, Mohammed V Military Hospital of Rabat, BP1018, Rabat 10100, Morocco.

出版信息

Gene. 2015 Aug 15;568(1):31-4. doi: 10.1016/j.gene.2015.05.010. Epub 2015 May 7.

DOI:10.1016/j.gene.2015.05.010

PMID:25958342

Abstract

BACKGROUND/AIMS: There is increasing evidence for the effect of rs12979860 IL28B polymorphism in response to the standard treatment PEG-IFN/RBV (i.e. combination of pegylated interferon and ribavirin) in chronic hepatitis C virus (HCV) infection. The present study aimed to determine the impact of IL28B associations in interferon responsiveness in 187 Moroccan patients with chronic HCV infection.

METHODS

HCV RNA levels were measured with a real-time RT-PCR assay and treatment efficacy was assessed by sustained virological response (SVR) and patients were classified as responders or non-responders. IL28B rs12979860 polymorphism genotyping was achieved by PCR-HRM technique.

RESULTS

The results demonstrated that SVR was achieved in 102 patients (55%); while 69 were non-responders (37%) and 16 relapsed (8%). Genotype 1 was the predominant HCV genotype detected in 112 patients followed by genotype 2 in 56 patients. The genotype CC was observed in 42 cases (25%); CT in 69 (41%) and TT in 57 (34%) demonstrating a C allele frequency of 46%. The SVR was observed in 32 patients with genotype CC accounting for 76%. The frequencies of rs12979860 CC type in infected individuals with HCV genotype 1 were 47% and 12% respectively in SVR and non-SVR groups. A highly statistically significant association between this SNP and SVR was found (p<0.001). Using multivariate logistic regression analysis, CC genotype was an independent factor for SVR. In the group of patients infected with genotype 2, SVR rate was 79%. The frequency of rs12979860 CC type in SVR group (n=4) was 9% and rs12979860 non-CC genotype was highly associated with SVR (p=0.001).

CONCLUSION

This finding adds evidence that genotyping for the IL-28B rs12979860 SNP can be a good parameter for the prediction of treatment success in patients with chronic hepatitis C before initiation of antiviral therapy in Morocco.

摘要

背景/目的：越来越多的证据表明，rs12979860白细胞介素28B（IL28B）基因多态性对慢性丙型肝炎病毒（HCV）感染患者接受聚乙二醇干扰素/利巴韦林（PEG-IFN/RBV，即聚乙二醇化干扰素与利巴韦林联合用药）标准治疗的疗效有影响。本研究旨在确定IL28B基因多态性对187例摩洛哥慢性HCV感染患者干扰素反应性的影响。

方法

采用实时逆转录聚合酶链反应（RT-PCR）检测HCV RNA水平，并通过持续病毒学应答（SVR）评估治疗效果，将患者分为应答者和无应答者。采用聚合酶链反应-高分辨率熔解曲线分析（PCR-HRM）技术对IL28B rs12979860基因多态性进行基因分型。

结果

结果显示，102例患者（55%）实现了SVR；69例为无应答者（37%），16例复发（8%）。112例患者中检测到的主要HCV基因型为1型，其次是56例患者为2型。42例（25%）观察到CC基因型；69例（41%）为CT基因型，57例（34%）为TT基因型，C等位基因频率为46%。32例CC基因型患者实现了SVR，占76%。HCV 1型感染个体中，rs12979860 CC型在SVR组和非SVR组中的频率分别为47%和12%。发现该单核苷酸多态性（SNP）与SVR之间存在高度统计学显著关联（p<0.001）。采用多因素逻辑回归分析，CC基因型是SVR的独立因素。在2型感染患者组中，SVR率为79%。SVR组（n=4）中rs12979860 CC型的频率为9%，rs12979860非CC基因型与SVR高度相关（p=0.001）。