The glutathione transferase Mu null genotype leads to lower 6-MMPR levels in patients treated with azathioprine but not with mercaptopurine

M M T J Broekman, D R Wong, G J A Wanten, H M Roelofs, C J van Marrewijk, O H Klungel, A L M Verbeek, P M Hooymans, H-J Guchelaar, H Scheffer, L J J Derijks, M J H Coenen, D J de Jong

Research output: Contribution to journalArticleAcademicpeer-review

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 × 10(8) 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(8) 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.The Pharmacogenomics Journal advance online publication, 3 January 2017; doi:10.1038/tpj.2016.87.

Original languageEnglish
Pages (from-to)160–166
Number of pages7
JournalPharmacogenomics Journal
Volume18
DOIs
Publication statusPublished - 2018

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