Vidal-Castiñeira Jose Ramón, López-Vázquez Antonio, Martínez-Borra Jesús, Martínez-Camblor Pablo, Prieto Jesús, López-Rodríguez Rosario, Sanz-Cameno Paloma, de la Vega Juan, Rodrigo Luis, Pérez-López Rosa, Pérez-Álvarez Ramón, López-Larrea Carlos
Immunology Service, Hospital Universitario Central de Asturias, Oviedo, Spain.
Oficina de Investigación Biosanitaria (OIB), Oviedo, Spain.
PLoS One. 2014 Jun 13;9(6):e99426. doi: 10.1371/journal.pone.0099426. eCollection 2014.
The aim of this study was to analyse the distribution of KIR haplotypes and the KIR2DL2/3 alleles in chronic HCV-infected patients in order to establish the influence on the response to pegylated interferon plus ribavirin classical treatment. The alleles study of previously associated KIR2DL2/3 showed that KIR2DL2001 was more frequent in non-SVR (NSVR) (42.2% vs. 27.5%, p<0.05) and KIR2DL3001 was associated with sustained viral response (SVR) (41.6% vs. 61.2%, p<0.005). The KIR2DL3*001-HLA-C1 association was also significant (24.5% vs. 45.7%, p<0.001). From the frequencies of KIR obtained, 35 genotypes were assigned on the basis of previous studies. The centromeric A/A genotype was more frequent in SVR (44.1% vs. 34.5%, p<0.005) and the centromeric B/B genotype was found to be significantly more frequent in NSVR (20.9% vs. 11.2%, p<0.001). The logic regression model showed the importance of KIR genes in predicting the response to combined treatment, since the positive predictive value (PPV) was improved (from 55.9% to 75.3%) when the analysis of KIR was included in addition to the IFNL3 rs12979860 polymorphism. The study of KIR receptors may be a powerful tool for predicting the combined treatment response in patients with chronic HCV infection in association with the determination of IFNL3 polymorphism.
本研究旨在分析慢性丙型肝炎病毒（HCV）感染患者中杀伤细胞免疫球蛋白样受体（KIR）单倍型和KIR2DL2/3等位基因的分布情况，以确定其对聚乙二醇干扰素联合利巴韦林传统治疗反应的影响。对先前相关的KIR2DL2/3等位基因的研究表明，KIR2DL2001在无持续病毒学应答（NSVR）患者中更为常见（42.2%对27.5%，p<0.05），而KIR2DL3001与持续病毒学应答（SVR）相关（41.6%对61.2%，p<0.005）。KIR2DL3*001与HLA-C1的关联也很显著（24.5%对45.7%，p<0.001）。根据获得的KIR频率，基于先前的研究确定了35种基因型。着丝粒A/A基因型在SVR患者中更为常见（44.1%对34.5%，p<0.005），着丝粒B/B基因型在NSVR患者中显著更为常见（20.9%对11.2%，p<0.001）。逻辑回归模型显示KIR基因在预测联合治疗反应中的重要性，因为在分析IFNL3 rs12979860多态性的基础上加入KIR分析后，阳性预测值（PPV）有所提高（从55.9%提高到75.3%）。KIR受体的研究可能是预测慢性HCV感染患者联合治疗反应的有力工具，同时结合IFNL3多态性的测定。
