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題 名 | The Association between Single-Nucleotide Polymorphisms in the Inosine Triphosphate Pyrophosphatase Gene and Ribavirin-induced Hemolytic Anemia in Genotype 2 Hepatitis C Virus-infected Taiwanese Patients Receiving Pegylated Interferon and Ribavirin Combination Therapy=感染第二型病毒基因型之C型肝炎病患接受長效型干擾素合併Ribavirin治療時,肌苷三磷酸焦磷酸酶(ITPA)基因之單一核苷酸多型性與溶血性貧血之相關性 |
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作 者 | 陳昇弘; 彭成元; 賴學洲; 林佳欣; 高榮達; 莊伯恒; 蘇文邦; 林志明; 陳景祥; | 書刊名 | 臺灣消化醫學雜誌 |
卷 期 | 30:3 2013.09[民102.09] |
頁 次 | 頁256-266 |
分類號 | 415.5332 |
關鍵詞 | 單一核苷酸多型性; 肌苷三磷酸焦磷酸酶; 溶血性貧血; C型肝炎病毒; Single-nucleotide polymorphisms; SNP; Inosine triphosphate pyrophosphatase; ITPA; Hemolytic anemia; Hepatitis C virus; |
語 文 | 英文(English) |
中文摘要 | 背景:最近的基因組關聯性研究報告指出,C型肝炎病患接受長效型干擾素(pegIFN)合併Ribavirin(RBV)治療時,肌苷三磷酸焦磷酸酶(ITPA)基因之單一核苷酸多型性(SNP)與溶血性貧血之間有顯著相關性。然而,有限的研究曾分析感染第二基因型C型肝炎病毒(HCV-2)之台灣患者。本研究旨在探討這些SNP,對貧血,血紅素(Hb)下降,以及治療效果的影響。材料與方法:共有二百三十五位符合資格的HCV-2感染患者接受合併治療24週。並從周邊血液單核球細胞基因組,分析位於20號染色體rs1127354位置的功能性ITPA基因變異。以確認重度貧血(血紅蛋白<10克/dL)和血紅素下降(≧4克/dL)的預測因子。結果:多變項邏輯斯回歸分析確定年齡(≧60歲)(odds ratio,OR,2.337;95%confidence interval,CI,1.180-4.627;P=0.015),女性(OR,3.463;95%CI,1.913-6.269,P<0.001),和ITPA rs1127354 C/C(OR,2.227;95%CI,1.168-4.247,P=0.015),可以獨立預測整個24週的治療過程中的嚴重貧血。男性(OR,2.224;95%CI,1.275-3.879;P=0.005) 和ITPA rs1127354 C/C(OR,3.135;95%CI,1.702-5.775;P<0.001),與血紅素下降相關。多變項Cox回歸分析顯示年齡(≧60歲)(hazard ratio,HR,1.915;95%CI,1.226-2.993;P=0.004), 女性(HR,2.712;95%CI,1.680-4.380;P<0.001),和ITPA rs1127354 C/C(HR,2.162;95%CI,1.302-3.590;P=0.003),亦可獨立預測整個24週的治療過程中的嚴重貧血。持續病毒學反應(SVR)和貧血或ITPA SNP不相關。結論:感染HCV-2之慢性C型肝炎台灣病患,接受合併治療時,ITPA SNP可預測RBV引起之溶血性貧血,以及血紅素下降,但並不影響SVR。 |
英文摘要 | Background: Genome-wide association studies have reported a significant association between single-nucleotide polymorphisms (SNP) in the inosine triphosphate pyrophosphatase (ITPA) gene and ribavirin (RBV)-induced anemia in hepatitis C virus (HCV)-infected patients receiving pegylated interferon (pegIFN) and RBV combination therapy. However, few studies have analyzed genotype 2 HCV (HCV-2)-infected Taiwanese patients.This study aimed to evaluate the effects of these polymorphisms on anemia, hemoglobin (Hb) decline, and treatment outcomes.Materials and Methods: Two hundred and thirty-five eligible HCV-2 infected Taiwanese participants received 24 weeks of therapy. Genomic DNA from peripheral blood mononuclear cells was genotyped for one functional ITPA variant on chromosome 20 (C/C, A/A or C/A, rs1127354). Predictors of severe anemia (Hb < 10 g/dL) and Hb decline (≧ 4 g/dL) were identified. Odds ratios (OR) and hazards ratios (HR) were determined based on a 95% confidence interval (CI).Results: Multivariate logistic regressions identified age (≧ 60 years) (OR, 2.337; CI, 1.180-4.627; P = 0.015), female gender (OR, 3.463; CI, 1.913-6.269; P < 0.001), and ITPA rs1127354 C/C (OR, 2.227; CI, 1.168-4.247; P = 0.015) as predictors of severe anemia throughout treatment. Male gender (OR, 2.224; CI, 1.275-3.879; P = 0.005) and ITPA rs1127354 C/C (OR, 3.135; CI, 1.702-5.775; P < 0.001) were associated with Hb decline. Multivariate Cox regression analysis also identified age (≧60 years) (HR, 1.915; CI, 1.226-2.993; P = 0.004), female gender (HR, 2.712; CI, 1.680-4.380; P < 0.001), and ITPA rs1127354 C/C (HR, 2.162; CI, 1.302-3.590; P = 0.003) as predictors of severe anemia. Sustained virological response (SVR) was not associated with anemia or ITPA SNP.Conclusions: In HCV-2 infected Taiwanese patients on combination therapy, ITPA SNP predicts RBV-induced hemolytic anemia, Hb decline, but does not affect the SVR. |
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