Hypoxanthine guanine phosphoribosyltransferase activity is related to 6-thioguanine nucleotide concentrations and thiopurine-induced leukopenia in the treatment of inflammatory bowel disease.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Liang Ding, Fang-bin Zhang, Hui Liu, Xiang Gao, Hui-chang Bi, Xue-ding Wang, Bai-li Chen, Yu Zhang, Li-zi Zhao, Guo-ping Zhong, Pin-jin Hu, Min-hu Chen, Ming Huang
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 18 Issue 1 Pg. 63-73 (Jan 2012) ISSN: 1536-4844 [Electronic] England
• PMID: 21381155 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Crohn's & Crohn's & Colitis Foundation of America, Inc.

Chemical References

• Methyltransferases
• thiopurine methyltransferase
• Hypoxanthine Phosphoribosyltransferase
• Thioguanine

Topics

• Adult
• Aged
• Erythrocytes (enzymology)
• Female
• Humans
• Hypoxanthine Phosphoribosyltransferase (metabolism)
• Inflammatory Bowel Diseases (metabolism, therapy)
• Leukopenia (chemically induced, genetics, metabolism)
• Male
• Methyltransferases (genetics, metabolism)
• Middle Aged
• Polymorphism, Genetic
• Prognosis
• Thioguanine (blood)