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ITPA 基因多态性(94C>A)对埃及慢性丙型肝炎患者治疗期间利巴韦林诱导性贫血的影响。

ITPA gene polymorphism (94C>A) effects on ribavirin-induced anemia during therapy in Egyptian patients with chronic hepatitis C.

机构信息

Department of Endemic Medicine and Hepatology, Kasr Al Ainy Hospital, School of Medicine, Cairo University, Cairo, Egypt.

Department of Tropical Medicine, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo, Egypt.

出版信息

J Med Virol. 2017 Oct;89(10):1823-1829. doi: 10.1002/jmv.24844. Epub 2017 May 29.

DOI:10.1002/jmv.24844
PMID:28480960
Abstract

Inosine triphosphatase (ITPA) gene variants can protect against ribavirin (RBV)-induced anemia in patients treated for chronic hepatitis C. The aim of this study was to determine the relationship between genetic variants of ITPA polymorphism, anemia, RBV dose reduction, and treatment response in hepatitis C virus (HCV)-infected patients. This study was conducted on 97 Egyptian chronic HCV patients who were scheduled for pegylated-interferon (PEG-INF) /RBV therapy. ITPA genotypes rs1127354 were determined by Real Time PCR melting curve analysis. Effects of ITPA polymorphism on hemoglobin (Hb) levels, RBV dose reduction and treatment response were analyzed. The homozygous wild genotype (CC) was associated with Hb reduction at week 4 (P = 0.004). The minor allele protected against Hb reduction. No association with sustained virological response was observed (P = 0.492). Female gender; lower baseline Hb and higher baseline WBC were associated with week 4 anemia (P = 0.04; P = 0.023; 0.033, respectively). The ITPA gene polymorphism rs1127354 heterozygous genotype (CA) may influence Hb levels and protect against hemolytic anemia during RBV-containing regimens for HCV. However, such findings were not significantly related to treatment outcomes. Patients with wild ITPA genotype (CC) experienced a more Hb drop and RBV dose reductions more frequently.

摘要

肌苷三磷酸酶 (ITPA) 基因变异可预防慢性丙型肝炎患者接受利巴韦林 (RBV) 治疗引起的贫血。本研究旨在确定 ITPA 多态性基因变异、贫血、RBV 剂量减少与丙型肝炎病毒 (HCV) 感染患者治疗反应之间的关系。本研究纳入了 97 名埃及慢性 HCV 患者,他们计划接受聚乙二醇干扰素 (PEG-INF)/RBV 治疗。通过实时 PCR 熔解曲线分析确定 ITPA 基因型 rs1127354。分析了 ITPA 多态性对血红蛋白 (Hb) 水平、RBV 剂量减少和治疗反应的影响。纯合野生基因型 (CC) 与第 4 周 Hb 下降有关 (P=0.004)。小等位基因可预防 Hb 下降。未观察到与持续病毒学应答相关 (P=0.492)。女性;较低的基线 Hb 和较高的基线白细胞计数与第 4 周贫血相关 (P=0.04;P=0.023;0.033)。ITPA 基因多态性 rs1127354 杂合基因型 (CA) 可能影响 Hb 水平,并在含有 RBV 的 HCV 治疗方案中预防溶血性贫血。然而,这些发现与治疗结果无显著相关性。野生型 ITPA 基因型 (CC) 的患者 Hb 下降更明显,更频繁地减少 RBV 剂量。

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