Hypoxanthine guanine phosphoribosyltransferase activity is related to 6-thioguanine nucleotide concentrations and thiopurine-induced leukopenia in the treatment of inflammatory bowel disease
Article first published online: 4 MAR 2011
Copyright © 2011 Crohn's & Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 1, pages 63–73, January 2012
How to Cite
Ding, L., Zhang, F.-b., Liu, H., Gao, X., Bi, H.-c., Wang, X.-d., Chen, B.-l., Zhang, Y., Zhao, L.-z., Zhong, G.-p., Hu, P.-j., Chen, M.-h. and Huang, M. (2012), Hypoxanthine guanine phosphoribosyltransferase activity is related to 6-thioguanine nucleotide concentrations and thiopurine-induced leukopenia in the treatment of inflammatory bowel disease. Inflamm Bowel Dis, 18: 63–73. doi: 10.1002/ibd.21676
- Issue published online: 11 DEC 2011
- Article first published online: 4 MAR 2011
- Manuscript Accepted: 13 JAN 2011
- Manuscript Received: 16 DEC 2010
- hypoxanthine guanine phosphoribosyltransferase (HPRT);
- thiopurine S-methyltransferase (TPMT);
- 6-thioguanine nucleotides (6-TGNs);
- thiopurine drug;
- inflammatory bowel disease (IBD)
Thiopurine drugs are widely used in the treatment of inflammatory bowel disease (IBD). The polymorphic enzyme thiopurine S-methyltransferase (TPMT) is of importance for thiopurine metabolism and adverse events occurrence. The role of other thiopurine-metabolizing enzymes is less well known. This study investigated the effects of TPMT and hypoxanthine guanine phosphoribosyltransferase (HPRT) activities on 6-thioguanine nucleotides (6-TGNs) concentrations and thiopurine-induced leukopenia in patients with IBD.
Clinical data and blood samples were collected from 120 IBD patients who were receiving azathioprine (AZA)/6-mercaptopurine (6-MP) therapy. Erythrocyte TPMT, HPRT activities and 6-TGNs concentrations were determined. HPRT activity and its correlation with TPMT activity, 6-TGNs level, and leukopenia were evaluated.
The HPRT activity of all patients ranged from 1.63–3.33 (2.31 ± 0.36) μmol/min per g Hb. HPRT activity was significantly higher in patients with leukopenia (27, 22.5%) than without (P < 0.001). A positive correlation between HPRT activity and 6-TGNs concentration was found in patients with leukopenia (r = 0.526, P = 0.005). Patients with HPRT activity > 2.70 μmol/min per g Hb could have an increased risk of developing leukopenia (odds ratio = 7.47, P < 0.001). No correlation was observed between TPMT activity and HPRT activity, 6-TGNs concentration, or leukopenia.
High levels of HPRT activity could be a predictor of leukopenia and unsafe 6-TGN concentrations in patients undergoing AZA/6-MP therapy. This could partly explain the therapeutic response or toxicity that could not be adequately explained by the polymorphisms of TPMT. (Inflamm Bowel Dis 2011;)