AOX1 and XDH Enzymes Genotyping and its Effect on Clinical Response to Azathioprine in Inflammatory Bowel Disease Patients Among Jordanian Population

Author(s): Sereen Mahasneh, Ahmad Sharab, Mohammad Al Shhab, Mohammad Rashid, Malek Zihlif*

Journal Name: Current Drug Metabolism

Volume 21 , Issue 2 , 2020

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background and Objectives: Inflammatory bowel disease (IBD) is a set of chronic inflammatory gastrointestinal disorders, which include ulcerative colitis (UC) and Crohn’s disease (CD) that affects many patients worldwide with a peak incidence in early adult life. The immunosuppressant drug Azathioprine (AZA) represents one of the most useful drugs in the management of IBD. It is metabolized by many enzymes like AOX1, and XDH enzymes, the variation in the metabolism of AZA may contribute to inter-individual variation in response to this treatment. This study aims to find out if there is an association between certain AOX1 and XDH polymorphisms and AZA response in Jordanian IBD patients.

Methods: One hundred IBD patients aged between (17-72) years and taking AZA were enrolled and genotyped for AOX13404G, XDH1936C and XDH2107C polymorphisms using DNA Sequencing (Sanger) method.

Results and Conclusion: This study revealed that 16% of our patients were non-responders to AZA; they needed an alternative therapy (biological agent) or steroids along with AZA. There was no statistically significant association (p-value>0.05) between the AOX1 3404G, XDH 1936C and XDH 2107C polymorphisms and the response to AZA among Jordanian IBD patients. Finally, the study showed an association between the age of the patient and the response to AZA (p-value=0.013).

Keywords: Azothioprine, AOX1, XDH, genotyping, inflammatory bowel disease, Jordanian.

Bouhnik, Y.; Scemama, G.; Taï, R.; Matuchansky, C.; Rambaud, J. C.; Lémann, M.; Mary, J. Y. Long-term follow-up of patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. Lancet, 1996, 347(8996), 215-219.
George, J.N.; Woolf, S.H.; Raskob, G.E. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood, 1996, 88(1), 3-40.
Derijks, L.J.J.; Gilissen, L.P.L.; Hooymans, P.M.; Hommes, D.W. Review article: thiopurines in inflammatory bowel disease. Aliment. Pharmacol. Ther., 2006, 24(5), 715-729.
Smith, M.A.; Marinaki, A.M.; Arenas, M.; Shobowale-Bakre, M.; Lewis, C.M.; Ansari, A.; Duley, J.; Sanderson, J.D. Novel pharmacogenetic markers for treatment outcome in azathioprine-treated inflammatory bowel disease. Aliment. Pharmacol. Ther., 2009, 30(4), 375-384.
[] [PMID: 19500084]
Sohrabpour, A.A.; Malekzadeh, R.; Keshavarzian, A. Current therapeutic approaches in inflammatory bowel disease. Curr. Pharm. Des., 2010, 16(33), 3668-3683.
Sands, B.E. Therapy of inflammatory bowel disease. Gastroenterology, 2000, 118(2)(Suppl. 1), S68-S82.
[] [PMID: 10868899]
Quetglas, E.G.; Mujagic, Z.; Wigge, S. Update on pathogenesis and predictors of response of therapeutic strategies used in inflammatory bowel disease. World J. Gastroenterol., 2015, 21(44), 12519.
Hartmann, T.; Terao, M.; Garattini, E.; Teutloff, C.; Alfaro, J.F.; Jones, J.P.; Leimkühler, S. The impact of single nucleotide polymorphisms on human aldehyde oxidase. Drug Metab. Dispos., 2012, 40(5), 856-864.
[] [PMID: 22279051]
Kudo, M.; Moteki, T.; Sasaki, T. Functional characterization of human xanthine oxidase allelic variants. Pharmacogenet. Genomics, 2008, 18(3), 243-251.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [140 - 144]
Pages: 5
DOI: 10.2174/1389200221666200413125011
Price: $65

Article Metrics

PDF: 23