Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
Mol Med Rep. 2012 Feb;5(2):517-20. doi: 10.3892/mmr.2011.659. Epub 2011 Nov 2.
Ribavirin (RBV)-induced anemia is a serious side effect of pegylated interferon (PEG-IFN) plus RBV therapy which is the standard care most effective for hepatitis C virus (HCV) infection. In the present study, we investigated the association of inosine triphosphate pyrophosphatase (ITPA) genotypes with RBV-induced hemoglobin (Hb) reduction in HCV patients treated with PEG-IFN/RBV therapy. The genotypes of the ITPA rs1127354 single nucleotide polymorphism were determined in 179 patients with HCV infection. Among them, 52 patients were treated with PEG-IFN/RBV. The frequency of the ITPA major allele (CC) was 76.3% and that of the minor allele (CA and AA) was 23.7%. A rapid decrease in Hb levels during the initial 4 weeks was observed in patients with the ITPA major allele (CC), but not in patients with the ITPA minor allele (C/A and AA). Hb levels at 4 weeks were significantly lower in patients with the ITPA major allele than the levels in patients with the minor allele. Out of the 41 patients, 6 (14.6%) with ITPA major allele had Hb levels <10 g/dl and 11 patients (26.8%) had a decline in Hb of >3 g/dl. None of the patients with the ITPA minor allele had such data. There were no significant differences in virological responses of HCV-RNA between patients with the ITPA major allele and those with the minor allele. In conclusion, the ITPA genotypes may be a useful marker for prediction of RBV-induced anemia.
利巴韦林（RBV）引起的贫血是聚乙二醇干扰素（PEG-IFN）加 RBV 治疗的严重副作用，这是治疗丙型肝炎病毒（HCV）感染最有效的标准治疗方法。在本研究中，我们研究了肌苷三磷酸焦磷酸酶（ITPA）基因型与聚乙二醇干扰素/利巴韦林治疗 HCV 患者的 RBV 诱导血红蛋白（Hb）下降的关系。在 179 例 HCV 感染患者中确定了 ITPA rs1127354 单核苷酸多态性的基因型。其中，52 例患者接受了 PEG-IFN/RBV 治疗。ITPA 主要等位基因（CC）的频率为 76.3%，次要等位基因（CA 和 AA）的频率为 23.7%。在携带 ITPA 主要等位基因（CC）的患者中，Hb 水平在最初的 4 周内迅速下降，但在携带 ITPA 次要等位基因（C/A 和 AA）的患者中则没有。在携带 ITPA 主要等位基因的患者中，第 4 周的 Hb 水平明显低于携带次要等位基因的患者。在 41 例患者中，6 例（14.6%）携带 ITPA 主要等位基因的患者 Hb 水平<10g/dl，11 例（26.8%）患者 Hb 下降>3g/dl。携带 ITPA 次要等位基因的患者均无此类数据。携带 ITPA 主要等位基因和携带次要等位基因的患者 HCV-RNA 的病毒学反应没有显著差异。总之，ITPA 基因型可能是预测 RBV 诱导性贫血的有用标志物。
