Abstract：
Thiopurines, an effective therapy for Crohn\'s disease (CD), often lead to adverse events (AEs). Gene polymorphisms affecting thiopurine metabolism may predict AEs. This retrospective study in CD patients (n = 114) with TPMT activity > 5 Units/Red Blood Cells analyzed TPMT (c.238 G > C, c.460 G > A, c.719 A > G), ITPA (c.94 C > A, IVS2 + 21 A > C), and NUDT15 (c.415 C > T) polymorphisms. All patients received azathioprine (median dose 2.2 mg/kg) with 41.2% experiencing AEs, mainly myelotoxicity (28.1%). No NUDT15 polymorphisms were found, 7% had TPMT, and 31.6% had ITPA polymorphisms. AEs led to therapy modifications in 41.2% of patients. Multivariate analysis identified advanced age (OR 1.046, p = 0.007) and ITPA IVS2 + 21 A > C (OR 3.622, p = 0.015) as independent predictors of AEs. IVS2 + 21 A > C was also associated with myelotoxicity (OR 2.863, p = 0.021). These findings suggest that ITPA IVS2 + 21 A > C polymorphism and advanced age predict AEs during thiopurine therapy for CD with intermediate-normal TPMT activity.
摘要：
硫嘌呤,克罗恩病（CD）的有效疗法，经常导致不良事件（AE）。影响硫嘌呤代谢的基因多态性可能预测AE。这项对TPMT活性>5单位/红细胞的CD患者（n=114）的回顾性研究分析了TPMT（c.238G>C，c.460G>A，c.719A>G)，ITPA（c.94C>A，IVS2+21A>C)，和NUDT15(c.415C>T)多态性。所有患者均接受硫唑嘌呤（中位剂量2.2mg/kg），41.2%出现不良事件，主要是骨髓毒性（28.1%）。没有发现NUDT15多态性，7%有TPMT，31.6%有ITPA多态性。AEs导致41.2%的患者治疗改变。多变量分析确定高龄（OR1.046，p=0.007）和ITPAIVS221A>C（OR3.622，p=0.015）是不良事件的独立预测因子。IVS2+21A>C也与骨髓毒性相关(OR2.863,p=0.021)。这些发现表明，ITPAIVS221A>C多态性和高龄可预测TPMT活性中等正常的CD的硫代嘌呤治疗期间的AE。
