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OAS1基因第7外显子rs10774671基因变异对埃及丙型肝炎病毒4型患者肝纤维化进展的影响

Impact of OAS1 Exon 7 rs10774671 Genetic Variation on Liver Fibrosis Progression in Egyptian HCV Genotype 4 Patients.

作者信息

Bader El Din Noha G, Anany Mohamed A, Dawood Reham M, Ibrahim Marwa K, El-Shenawy Reem, El Abd Yasmin S, El Awady Mostafa K

机构信息

Department of Microbial Biotechnology, National Research Centre , Giza, Egypt .

出版信息

Viral Immunol. 2015 Nov;28(9):509-16. doi: 10.1089/vim.2015.0041. Epub 2015 Oct 27.

Abstract

The aim of this study was to assess the impact of genetic variants of oligoadenylate synthetase 1 (OAS1) single-nucleotide polymorphism (SNP) rs10774671 at the exon 7 splice acceptor site on liver fibrosis progression and hepatitis C virus (HCV) outcome in Egyptian HCV genotype 4 patients. In this study, 195 subjects were enrolled; 60 controls and 135 chronic HCV genotype 4 patients with different fibrosis grades. All subjects were genotyped for OAS1 SNP rs10774671 polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. There was an increasing trend of liver fibrosis progression as 52.9% GG, 73.6% GA, and 83.3% AA genotypes were detected in late fibrosis patients (p = 0.025). The AA genotype was higher in the late fibrosis group than in the early fibrosis group (83.3% vs. 16.7%) (p = 0.001). The A allele was significantly affecting the liver fibrosis progression rate, more than the G allele (p = 0.001). The multivariate analysis showed that the OAS1 GA and AA genotypes were independent factors associated with liver progression (p = 0.009, odds ratio [OR] 3.467, 95% confidence interval [CI] 1.273-7.584). In addition, the A allele was associated with liver fibrosis progression (p = 0.014, OR 2.525, 95% CI 1.157-4.545). The polymorphism at OAS1 exon 7 rs3741981 might be a potential genetic marker and can be useful in the assessment of liver fibrosis progression and disease outcome in HCV-infected patients.

摘要

本研究的目的是评估外显子7剪接受体位点的寡腺苷酸合成酶1(OAS1)单核苷酸多态性(SNP)rs10774671的基因变异对埃及丙型肝炎病毒(HCV)基因4型患者肝纤维化进展和HCV转归的影响。在本研究中,纳入了195名受试者;60名对照者和135名不同纤维化分级的慢性HCV基因4型患者。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析对所有受试者进行OAS1 SNP rs10774671多态性基因分型。肝纤维化进展呈上升趋势,因为在晚期纤维化患者中检测到52.9%的GG基因型、73.6%的GA基因型和83.3%的AA基因型(p = 0.025)。晚期纤维化组的AA基因型高于早期纤维化组(83.3%对16.7%)(p = 0.001)。A等位基因对肝纤维化进展率的影响显著大于G等位基因(p = 0.001)。多变量分析显示,OAS1的GA和AA基因型是与肝进展相关的独立因素(p = 0.009,比值比[OR] 3.467,95%置信区间[CI] 1.273 - 7.584)。此外,A等位基因与肝纤维化进展相关(p = 0.014,OR 2.525,95% CI 1.157 - 4.545)。OAS1外显子7 rs3741981处的多态性可能是一种潜在的遗传标志物,可用于评估HCV感染患者的肝纤维化进展和疾病转归。

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