Lack of association between the ITPA 94C>A polymorphism and adverse effects from azathioprine.

Richard B Gearry, Rebecca L Roberts, Murray L Barclay, Martin A Kennedy
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引用次数: 114

Abstract

A 94C>A missense mutation in the ITPA gene which encodes inosine triphosphate pyrophosphatase has been associated with adverse effects from azathioprine, specifically flu-like symptoms, pancreatitis and rash. We hypothesized that this association may also be present in a larger, population-based group of inflammatory bowel disease patients intolerant of thiopurine drugs. We performed genotyping for this polymorphism and TPMT*2 and TPMT*3 in 73 such patients and 74 patients with inflammatory bowel disease who have tolerated azathioprine. We could not demonstrate a significant association between the ITPA94C>A genotype and any adverse effects (Odds ratio (OR) 1.015, 95% confidence interval (CI) 0.360-2.867, P = 0.593), flu-like symptoms (OR 1.547, 95%CI 0.368-6.496, P = 0.398), rash (no ITPA 94C>A polymorphism identified) or pancreatitis (no ITPA 94C>A polymorphism identified). We found no significant association between the ITPA 94C>A polymorphism and adverse effects to thiopurine drugs.

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ITPA 94C>A 多态性与硫唑嘌呤的不良反应之间缺乏关联。
编码三磷酸肌苷焦磷酸酶的 ITPA 基因中的 94C>A 错义突变与硫唑嘌呤的不良反应有关,特别是流感样症状、胰腺炎和皮疹。我们推测,这种关联也可能存在于不耐受硫嘌呤类药物的更大范围的炎症性肠病患者群体中。我们对 73 名此类患者和 74 名能耐受硫唑嘌呤的炎症性肠病患者进行了该多态性以及 TPMT*2 和 TPMT*3 的基因分型。我们无法证明 ITPA94C>A 基因型与任何不良反应(Odds ratio (OR) 1.015,95% 置信区间 (CI)0.360-2.867,P = 0.593)、流感样症状(OR 1.547,95%CI 0.368-6.496,P = 0.398)、皮疹(未发现 ITPA 94C>A 多态性)或胰腺炎(未发现 ITPA 94C>A 多态性)之间存在显著关联。我们发现 ITPA 94C>A 多态性与硫嘌呤类药物的不良反应无明显关联。
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