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Mx A基因单核苷酸多态性与埃及丙型肝炎病毒4型患者对聚乙二醇干扰素和利巴韦林治疗反应性之间的关系评估。

Assessment of the Relation Between SNP in MxA Gene and the Responsiveness of Egyptian HCV Genotype 4 Patients to Pegylated Interferon and Ribavirin Treatment.

作者信息

Hassany Mohamed, Gamal Amany, Zaki Nashwa, Eysa Basem

机构信息

Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.

Department of Clinical Pathology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.

出版信息

Gastroenterology Res. 2017 Apr;10(2):100-105. doi: 10.14740/gr810w. Epub 2017 Apr 19.

Abstract

BACKGROUND

Pegylated interferon (PegIFN) is used in the treatment of chronic hepatitis C virus (HCV) patients especially in resource limited countries. Treatment with PegIFN stimulates the expression of a number of host genes encoding enzymes with antiviral activities, including myxovirus resistance gene-A (MxA gene). MxA gene was found to have a single nucleotide polymorphism (SNP) at position -88 in the promoter region that affects the expression of MxA gene protein and was suggested to affect the treatment outcome. The aim of the work was to assess the relation between the SNP in the MxA gene and its impact on treatment of chronic HCV patients with PegIFN and ribavirin.

METHODS

We therefore genotyped the biallelic G/T SNP in the promoter region of MxA gene at position -88 from the transcription start site by restriction fragment length polymorphism (RFLP) in 70 chronic HCV genotype 4 interferon naive Egyptians and 40 healthy controls.

RESULTS

G allele was the prevalent one in both HCV patients group (105, 74.5%) and control group (66, 82.5%), while T allele was less expressed in patients group (36, 25.5%) and control group (14, 17.5%). There is no correlation between genotypes and response to IFN-alpha therapy: GG (OR: 0.958, 95% CI: 0.541 - 1.698, P = 0.884), GT (OR: 0.667, 95% CI: 0.188 - 2.362, P = 0.530), and TT (OR: 0.300, 95% CI: 0.083 - 1.090, P = 0.067).

CONCLUSION

MxA nt-88 SNP did not affect the sustained virological response (SVR) rates after PegIFN and ribavirin combined treatment and did not act as a biological marker to potentially identify responders and non-responders to treatment. Our results call for additional large studies and/or meta-analysis of all currently available data to examine the role of MxA nt-88 SNP in predicting response to PegIFN and ribavirin in patients with IFN-alpha naive HCV genotype 4.

摘要

背景

聚乙二醇化干扰素(PegIFN)用于治疗慢性丙型肝炎病毒(HCV)患者,尤其是在资源有限的国家。PegIFN治疗可刺激许多编码具有抗病毒活性酶的宿主基因表达,包括黏液病毒抗性基因A(MxA基因)。研究发现,MxA基因启动子区域-88位存在单核苷酸多态性(SNP),该多态性影响MxA基因蛋白的表达,并被认为会影响治疗效果。本研究旨在评估MxA基因中的SNP及其对PegIFN联合利巴韦林治疗慢性HCV患者的影响。

方法

因此,我们采用限制性片段长度多态性(RFLP)方法,对70例慢性HCV基因4型初治埃及患者和40例健康对照者的MxA基因启动子区域转录起始位点-88位的双等位基因G/T SNP进行基因分型。

结果

G等位基因在HCV患者组(105例,74.5%)和对照组(66例,82.5%)中均占优势,而T等位基因在患者组(36例,25.5%)和对照组(14例,17.5%)中的表达较少。基因型与干扰素α治疗反应之间无相关性:GG(OR:0.958,95%CI:0.541 - 1.698,P = 0.884)、GT(OR:0.667,95%CI:0.188 - 2.362,P = 0.530)和TT(OR:0.300,95%CI:0.083 - 1.090,P = 0.067)。

结论

MxA基因nt-88 SNP不影响PegIFN联合利巴韦林治疗后的持续病毒学应答(SVR)率,也不能作为潜在识别治疗应答者和无应答者的生物学标志物。我们的研究结果呼吁进行更多大规模研究和/或对所有现有数据进行荟萃分析,以探讨MxA基因nt-88 SNP在预测初治HCV基因4型患者对PegIFN和利巴韦林治疗反应中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e689/5412542/a4591a77862c/gr-10-100-g001.jpg

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