Guzmán-Fulgencio M, Berenguer J, Pineda-Tenor D, Jiménez-Sousa M A, García-Álvarez M, Aldámiz-Echevarria T, Carrero A, Diez C, Tejerina F, Vázquez S, Briz V, Resino S
Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III (Campus Majadahonda), Carretera Majadahonda-Pozuelo, Km 2.2, 28220, Majadahonda, Madrid, Spain.
Eur J Clin Microbiol Infect Dis. 2015 Feb;34(2):385-93. doi: 10.1007/s10096-014-2245-1. Epub 2014 Sep 19.
Interleukin-7 (IL-7) is a critical factor in maintaining or inducing effective antiviral CD4+ and CD8+ T-cell responses. The aim of this study was to examine the association of interleukin-7 receptor-α (IL7RA) polymorphisms with a sustained virologic response (SVR) after hepatitis C virus (HCV) therapy with pegylated interferon-alpha plus ribavirin (pegIFNα/ribavirin) in 177 human immunodeficiency virus (HIV)/HCV-coinfected patients. We performed a retrospective study in 177 naïve patients who started HCV treatment. The IL7RA rs6897932, rs987106, and rs3194051 polymorphisms were genotyped by the GoldenGate® assay. An SVR was defined as undetectable HCV viral load through 24 weeks after the end of HCV treatment. The highest SVR rate was found in patients with the rs6897932 CC (p = 0.029) and rs3194051 GG (p = 0.002) genotypes, and HCV genotypes 2/3 (GT2/3) infected patients with the rs987106 AA genotype (p = 0.048). Additionally, carriers of the rs3194051 GG genotype had a higher likelihood of achieving an SVR [adjusted odds ratio (aOR) = 5.32; 95 % confidence interval (CI) = 1.07-26.94; p = 0.040] than patients with the rs3194051 AA/AG genotype, while rs6897932 CC (aOR = 0.63; p = 0.205) and rs987106 AA (aOR = 0.60; p = 0.213) were not significant. Moreover, three major haplotypes were found: 46.6 % for CTA, 32.4 % for CAG, and 20.7 % for TAA haplotypes. Patients infected with GT2/3 and carriers of the CTA haplotype had lower odds of achieving an SVR (aOR = 0.08; p = 0.004) and the CAG haplotype (favorable alleles) had higher odds of achieving an SVR than other haplotypes (aOR = 21.96; p < 0.001). IL7RA polymorphisms seem to play a significant role in the virological response to pegIFNα/ribavirin therapy in HIV/HCV-coinfected patients, in particular among patients infected with HCV GT2/3.
白细胞介素-7(IL-7)是维持或诱导有效的抗病毒CD4⁺和CD8⁺T细胞反应的关键因素。本研究的目的是在177例人类免疫缺陷病毒(HIV)/丙型肝炎病毒(HCV)合并感染患者中,检测白细胞介素-7受体-α(IL7RA)基因多态性与聚乙二醇化干扰素-α加利巴韦林(pegIFNα/利巴韦林)治疗HCV后持续病毒学应答(SVR)之间的关联。我们对177例开始HCV治疗的初治患者进行了一项回顾性研究。通过GoldenGate®检测法对IL7RA rs6897932、rs987106和rs3194051基因多态性进行基因分型。SVR定义为HCV治疗结束后24周时HCV病毒载量检测不到。rs6897932 CC基因型(p = 0.029)和rs3194051 GG基因型(p = 0.002)的患者以及HCV基因型2/3(GT2/3)感染且rs987106 AA基因型的患者(p = 0.048)的SVR率最高。此外,rs3194051 GG基因型携带者实现SVR的可能性高于rs3194051 AA/AG基因型患者[调整优势比(aOR)= 5.32;95%置信区间(CI)= 1.07 - 26.94;p = 0.040],而rs6897932 CC(aOR = 0.63;p = 0.205)和rs987106 AA(aOR = 0.60;p = 0.213)则无显著差异。此外,发现了三种主要单倍型:CTA为46.6%,CAG为32.4%,TAA单倍型为20.7%。感染GT2/3的患者和CTA单倍型携带者实现SVR的几率较低(aOR = 0.08;p = 0.004),而CAG单倍型(有利等位基因)实现SVR的几率高于其他单倍型(aOR = 21.96;p < 0.001)。IL7RA基因多态性似乎在HIV/HCV合并感染患者对pegIFNα/利巴韦林治疗的病毒学应答中起重要作用,尤其是在感染HCV GT2/3的患者中。