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巴基斯坦人群中OAS1基因第7外显子剪接受体位点多态性与丙型肝炎病毒感染干扰素治疗的相关性

Correlation of OAS1 gene polymorphism at exon 7 splice accepter site with interferon-based therapy of HCV infection in Pakistan.

作者信息

Imran Muhammad, Manzoor Sobia, Khattak Nasir Mahmood, Tariq Muqddas, Khalid Madiha, Javed Farakh, Bhatti Shameem

机构信息

Atta-ur-Rahman School of Applied Bio-Sciences, National University of Sciences and Technology , Islamabad 44000, Pakistan .

出版信息

Viral Immunol. 2014 Apr;27(3):105-11. doi: 10.1089/vim.2013.0107. Epub 2014 Mar 27.

Abstract

The most useful treatment for HCV infection worldwide is peg-interferon plus ribavirin, although the response varies from person to person. Hence, host genetics are significantly involved in the treatment response to HCV infection. The 2'-5' oligoadenylate synthetase (OAS) is one of the most important components of the immune system having significant antiviral functions. The aim of this study was to investigate the role of single nucleotide polymorphism (SNP) at the exon 7 splice acceptor site (SAS) of OAS1 to interferon-based therapy of HCV infection. OAS1 genotyping was performed in 140 HCV patients by restriction fragment length polymorphism polymerase chain reaction method (RFLP-PCR). These patients were enrolled for the study in 2010-2013. OAS1 SNP was also established in 120 healthy controls. Correlation of HCV genotypes, OAS1 SNP, and other factors with response to interferon therapy were statistically analyzed by SPSS 13 software. There were no significant differences in the distribution of OAS1 genotypes between healthy and patients subjects. The distribution of AG and AA genotypes of OAS1 genotypes between sustained virological responders (SVRs) and the non-responders (NRs) group were also comparable. However, Pearson chi square analysis indicated that the patients possessing a GG genotype of the OAS1 gene at exon 7 SAS demonstrated significantly positive association with treatment response to HCV infection (p=0.039). This study determined that SNP at exon 7 SAS of OAS1 was significantly associated with response to interferon-based therapy of HCV infection in our population.

摘要

在全球范围内,丙型肝炎病毒(HCV)感染最有效的治疗方法是聚乙二醇干扰素联合利巴韦林,不过治疗反应因人而异。因此,宿主基因在HCV感染的治疗反应中起着重要作用。2'-5'寡腺苷酸合成酶(OAS)是免疫系统最重要的组成部分之一,具有重要的抗病毒功能。本研究的目的是调查OAS1基因第7外显子剪接受体位点(SAS)的单核苷酸多态性(SNP)在基于干扰素的HCV感染治疗中的作用。通过限制性片段长度多态性聚合酶链反应法(RFLP-PCR)对140例HCV患者进行OAS1基因分型。这些患者于2010年至2013年纳入本研究。同时也对120名健康对照者进行了OAS1 SNP检测。使用SPSS 13软件对HCV基因型、OAS1 SNP及其他因素与干扰素治疗反应的相关性进行统计学分析。健康受试者和患者之间OAS1基因型的分布没有显著差异。持续病毒学应答者(SVRs)组和无应答者(NRs)组之间OAS1基因型的AG和AA基因型分布也具有可比性。然而,Pearson卡方分析表明,在第7外显子SAS处具有OAS1基因GG基因型的患者与HCV感染治疗反应呈显著正相关(p = 0.039)。本研究确定,在我们的研究人群中,OAS1基因第7外显子SAS处的SNP与基于干扰素的HCV感染治疗反应显著相关。

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