Open AccessNonsynonymous Polymorphism in Guanine Monophosphate Synthetase Is a Risk Factor for Unfavorable Thiopurine Metabolite Ratios in Patients With Inflammatory Bowel Disease
Author(s) -
Rebecca L. Roberts,
Mary Wallace,
Margien L. Seinen,
Adriaan A. van Bodegraven,
Krupa Krishnaprasad,
Gregory T. Jones,
André M. van Rij,
Angela Baird,
Ian C. Lawrance,
Ruth Prosser,
Peter A. Bampton,
Rachel Grafton,
Lisa A. Simms,
Corrie Studd,
Sally Bell,
Martin A. Kennedy,
Jacob Halliwell,
Richard B. Gearry,
Graham RadfordSmith,
Jane M. Andrews,
Patrick McHugh,
Murray L. Barclay
Publication year - 2018
Publication title -
inflammatory bowel diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.932
H-Index - 146
eISSN - 1536-4844
pISSN - 1078-0998
DOI - 10.1093/ibd/izy163
Subject(s) - thiopurine methyltransferase , nonsynonymous substitution , inflammatory bowel disease , metabolite , guanine , medicine , disease , inflammatory bowel diseases , gastroenterology , chemistry , biochemistry , gene , nucleotide , genome
Up to 20% of patients with inflammatory bowel disease (IBD) who are refractory to thiopurine therapy preferentially produce 6-methylmercaptopurine (6-MMP) at the expense of 6-thioguanine nucleotides (6-TGN), resulting in a high 6-MMP:6-TGN ratio (>20). The objective of this study was to evaluate whether genetic variability in guanine monophosphate synthetase (GMPS) contributes to preferential 6-MMP metabolizer phenotype.
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