| Literature DB >> 28045129 |
M M T J Broekman1, D R Wong2, G J A Wanten1, H M Roelofs1, C J van Marrewijk3, O H Klungel4, A L M Verbeek5, P M Hooymans2, H-J Guchelaar6, H Scheffer3, L J J Derijks7, M J H Coenen3, D J de Jong1.
Abstract
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 × 108 RBCs; P<0.01). In patients on MP (control group) 6-MMPR levels were comparable (6195 (1551-10712) versus 6544 (1717-11600) pmol/8 × 108 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.Entities:
Mesh：
Substances：
Year: 2017 PMID： 28045129 DOI： 10.1038/tpj.2016.87
Source DB: PubMed Journal: Pharmacogenomics J ISSN： 1470-269X Impact factor: 3.550