Tipu Imran, Marriage Fiona, Farooqi Zia-Ur-Rahman, Platt Hazel, Athar Muhammad Amin, Day Philip John, Short Andrea
Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan ; Manchester Institute of Biotechnology, University of Manchester, Manchester, UK.
Manchester Institute of Biotechnology, University of Manchester, Manchester, UK ; Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, UK.
Hepat Mon. 2014 Mar 9;14(3):e15076. doi: 10.5812/hepatmon.15076. eCollection 2014 Mar.
Polymorphisms in the interferon λ (INF λ) genes on chromosome 19 have been associated with clearance of hepatitis C virus (HCV) induced by interferon and ribavirin therapy however there is no such data available for Pakistani patients with HCV infection.
In this study, the effects of single nucleotide polymorphisms (SNPs) have been investigated in response to treatment with interferon-α and ribavirin in a cohort of 75 HCV genotype 3a patients.
A total number of 50 SNPs from the Interferon λ region on chromosome 19 were genotyped to investigate allelic associations with the treatment response in HCV type 3a patients. Thirteen SNPs were associated with HCV clearance, with the most significant alleles being RS8109886 (Fisher's P = 0.0001), RS8113007 (Fisher's P = 0.0001) and RS12979860 (Fisher's P = 0.0002).
These SNPs were found to be the most suitable SNPs for predicting treatment response in the present study. These findings support those reported previously. This could be used to improve HCV treatment strategies and suggest that Pakistani patients should be genotyped for the relevant SNPs to identify the patients who are more likely to respond to interferon and ribavirin therapy.
This therapy is costly and can be accompanied by several adverse side-effects, hence pre-treatment prediction of patients who are most likely to benefit would have both economic and patient benefits in the long term.
19号染色体上的干扰素λ(INFλ)基因多态性与干扰素和利巴韦林治疗诱导的丙型肝炎病毒(HCV)清除有关,然而,尚无针对巴基斯坦HCV感染患者的此类数据。
在本研究中,对75例HCV 3a基因型患者队列中,研究了单核苷酸多态性(SNP)对干扰素-α和利巴韦林治疗反应的影响。
对19号染色体上干扰素λ区域的总共50个SNP进行基因分型,以研究与HCV 3a型患者治疗反应的等位基因关联。13个SNP与HCV清除有关,最显著的等位基因为RS8109886(Fisher's P = 0.0001)、RS8113007(Fisher's P = 0.0001)和RS12979860(Fisher's P = 0.0002)。
在本研究中,这些SNP被发现是预测治疗反应最合适的SNP。这些发现支持了先前报道的结果。这可用于改进HCV治疗策略,并表明巴基斯坦患者应进行相关SNP的基因分型,以识别更可能对干扰素和利巴韦林治疗有反应的患者。
这种治疗成本高昂,且可能伴有多种不良副作用,因此,对最可能受益患者的治疗前预测从长期来看将对经济和患者都有益处。