谷胱甘肽转移酶Mu基因缺失型导致接受硫唑嘌呤而非巯嘌呤治疗的患者6-甲巯基嘌呤核糖核苷（6-MMPR）水平降低。
The glutathione transferase Mu null genotype leads to lower 6-MMPR levels in patients treated with azathioprine but not with mercaptopurine.
作者信息
Broekman M M T J, Wong D R, Wanten G J A, Roelofs H M, van Marrewijk C J, Klungel O H, Verbeek A L M, Hooymans P M, Guchelaar H-J, Scheffer H, Derijks L J J, Coenen M J H, de Jong D J
机构信息
Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Department of Gastroenterology, Nijmegen, The Netherlands.
Department of Clinical Pharmacy, Pharmacology and Toxicology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands.
出版信息
Pharmacogenomics J. 2018 Jan;18(1):160-166. doi: 10.1038/tpj.2016.87. Epub 2017 Jan 3.
The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-TGN) metabolite levels. We included 199 patients with inflammatory bowel disease (126 on AZA and 73 on MP). GSTM1-null genotype carriers on AZA had two-fold lower 6-MMPR levels than AZA users carrying one or two copies of GSTM1 (2239 (1006-4587) versus 4371 (1897-7369) pmol/8 × 10 RBCs; P<0.01). In patients on MP (control group) 6-MMPR levels were comparable (6195 (1551-10712) versus 6544 (1717-11600) pmol/8 × 10 RBCs; P=0.84). The 6-TGN levels were not affected by the GSTM1 genotype. The presence of genetic variants in GSTA1 and GSTA2 was not related to the 6-MMPR and 6-TGN levels.
硫唑嘌呤（AZA）向巯嘌呤（MP）的转化由谷胱甘肽转移酶Mu1（GSTM1）、α1（GSTA1）和α2（GSTA2）介导。我们利用TOPIC试验的数据设计了一项病例对照研究，以探讨基因变异对稳态6-甲基巯嘌呤核糖核苷酸（6-MMPR）和6-硫鸟嘌呤核苷酸（6-TGN）代谢物水平的影响。我们纳入了199例炎症性肠病患者（126例使用AZA，73例使用MP）。使用AZA的GSTM1基因缺失型基因型携带者的6-MMPR水平比携带一份或两份GSTM1拷贝的AZA使用者低两倍（2239（1006 - 4587）对4371（1897 - 7369）pmol/8×10红细胞；P<0.01）。在使用MP的患者（对照组）中，6-MMPR水平相当（6195（1551 - 10712）对6544（1717 - 11600）pmol/8×10红细胞；P = 0.84）。6-TGN水平不受GSTM1基因型的影响。GSTA1和GSTA2基因变异的存在与6-MMPR和6-TGN水平无关。
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