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TPMT genetic variants are associated with increased rejection with azathioprine use in heart transplantation

机译：TPMT基因变异与心脏移植中硫唑嘌呤的排斥反应增加有关

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Objectives Azathioprine (AZA) is an important immunosuppressant drug used in heart transplantation (HTX). Consensus guidelines recommend that patients with thiopurine S-methyltransferase (TPMT) genetic variants be started on lower AZA dose because of higher active metabolite levels and risk of adverse events. However, in-vitro lymphocyte proliferation assays performed in participants with inactive TPMT alleles have suggested that AZA use may result in decreased immunosuppressant efficacy as compared with wild-type (WT) individuals. The objective of this study was therefore to determine the effect of TPMT genetic variation on AZA efficacy or prevention of rejection in HTX recipients treated with AZA.Participants and methods We genotyped 93 HTX recipients treated with AZA and measured erythrocyte TPMT enzyme activity. Acute rejection was monitored by routine endomyocardial biopsies.
机译：目的硫唑嘌呤（AZA）是一种重要的免疫抑制剂，用于心脏移植（HTX）。共识性指南建议，由于较高的活性代谢产物水平和发生不良事件的风险，因此应以较低的AZA剂量开始具有硫嘌呤S-甲基转移酶（TPMT）基因变异的患者。但是，在具有无效TPMT等位基因的参与者中进行的体外淋巴细胞增殖试验表明，与野生型（WT）个体相比，使用AZA可能会导致免疫抑制功效降低。因此，本研究的目的是确定TPMT基因变异对AZA治疗的HTX受体的AZA功效或预防排斥的影响。参与者和方法我们对93名接受AZA治疗的HTX受体进行基因分型，并测量了红细胞TPMT酶的活性。通过常规的心肌内膜活检监测急性排斥反应。

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