Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain.
PLoS One. 2010 Oct 29;5(10):e13771. doi: 10.1371/journal.pone.0013771.
Recent genome-wide association studies report that the SNP rs8099917, located 8.9 kb upstream of the start codon of IL28B, is associated with both disease chronicity and therapeutic response to pegIFN-α and RBV in patients infected with genotype 1 HCV. To determine the effect of rs8099917 variation on the response of HCV to therapy, we genotyped this variant in a cohort of 160 HCV/HIV-1 coinfected patients in our clinic unit who received combined peg-IFN-α/RBV therapy. The rs8099917 T/G or G/G genotypes were observed in 56 patients (35%). Treatment failure occurred in 80% of G-allele carriers versus 48% of non-carriers (P<0.0001). This result reveals that the G allele was strongly associated with treatment failure in this patient cohort. Importantly, a highly significant association was found between the G-allele and response to therapy in HCV genotype 1-infected patients (P<0.0001) but not in HCV genotype 3-infected patients. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated that the rs8099917 TT genotype was a strong predictor of treatment success (5.83; 1.26-26.92; P = 0.021), independent of baseline plasma HCV-RNA load less than 500 000 IU/ml (4.85; 1.18-19.95; P = 0.025) and absence of advanced liver fibrosis (5.24; 1.20-22.91; P = 0.025). These results reveal the high prevalence of the rs8099917 G allele in HCV/HIV-1 coinfected patients as well as its strong association with treatment failure in HCV genotype 1-infected patients. rs8099917 SNP genotyping may be a valid pre-treatment predictor of which patients are likely to respond to treatment in this group of difficult-to-treat HCV/HIV-infected patients.
最近的全基因组关联研究报告称，位于 IL28B 起始密码子上游 8.9kb 处的 SNP rs8099917 与基因型 1 HCV 感染患者的疾病慢性化和聚乙二醇干扰素-α和利巴韦林治疗反应均相关。为了确定 rs8099917 变异对 HCV 治疗反应的影响，我们对我们临床单位的 160 名 HCV/HIV-1 合并感染患者进行了该变体的基因分型，这些患者接受了聚乙二醇干扰素-α/利巴韦林联合治疗。rs8099917 的 T/G 或 G/G 基因型在 56 名患者（35%）中观察到。G 等位基因携带者的治疗失败率为 80%，而非携带者为 48%（P<0.0001）。这一结果表明，在该患者队列中，G 等位基因与治疗失败强烈相关。重要的是，在 HCV 基因型 1 感染患者中发现 G 等位基因与治疗反应之间存在高度显著的关联（P<0.0001），但在 HCV 基因型 3 感染患者中则没有。多变量分析（比值比；95%置信区间；P 值）表明，rs8099917 TT 基因型是治疗成功的有力预测因子（5.83；1.26-26.92；P = 0.021），独立于基线血浆 HCV-RNA 载量小于 500000IU/ml（4.85；1.18-19.95；P = 0.025）和无晚期肝纤维化（5.24；1.20-22.91；P = 0.025）。这些结果表明，rs8099917 G 等位基因在 HCV/HIV-1 合并感染患者中的高流行率及其与 HCV 基因型 1 感染患者治疗失败的强烈关联。rs8099917 SNP 基因分型可能是治疗这种难以治疗的 HCV/HIV 感染患者群体中哪些患者可能对治疗有反应的有效治疗前预测因子。
