Roberts Rebecca L, Barclay Murray L
Department of Surgical Sciences, Dunedin School of Medicine, PO Box 56, Dunedin, New Zealand.
Department of Medicine, University of Otago Christchurch, PO Box 4345, Christchurch, New Zealand.
Pharmacogenomics. 2015 Jul;16(8):891-903. doi: 10.2217/pgs.15.29. Epub 2015 Jun 12.
Azathioprine and 6-mercaptopurine remain pivotal therapies for the maintenance of disease remission in patients with Crohn's disease and ulcerative colitis. While thiopurine S-methyltransferase deficiency was the first pharmacogenetic phenomenon to be recognized to influence thiopurine toxicity and reliably predict leukopenia, it does not predict other adverse effects, nor does it explain most cases of thiopurine resistance. In recent years, a number of other genetic polymorphisms have received increasing attention in the literature. In particular, SNPs in NUDT15 and in the class II HLA locus have been shown to predict thiopurine-related leukopenia and pancreatitis. The aim of this review is to provide a concise update of genetic variability which may influence patient response to azathioprine and 6-mercaptopurine.
硫唑嘌呤和6-巯基嘌呤仍然是克罗恩病和溃疡性结肠炎患者维持疾病缓解的关键疗法。虽然硫嘌呤S-甲基转移酶缺乏是首个被确认影响硫嘌呤毒性并可靠预测白细胞减少的药物遗传学现象，但它并不能预测其他不良反应，也无法解释大多数硫嘌呤耐药病例。近年来，许多其他基因多态性在文献中受到越来越多的关注。特别是，NUDT15和II类人白细胞抗原（HLA）基因座中的单核苷酸多态性（SNP）已被证明可预测硫嘌呤相关的白细胞减少和胰腺炎。本综述的目的是简要介绍可能影响患者对硫唑嘌呤和6-巯基嘌呤反应的基因变异性。
