Open AccessHypoxanthine guanine phosphoribosyltransferase activity is related to 6‐thioguanine nucleotide concentrations and thiopurine‐induced leukopenia in the treatment of inflammatory bowel disease
Author(s) -
Ding Liang,
Zhang Fangbin,
Liu Hui,
Gao Xiang,
Bi Huichang,
Wang Xueding,
Chen Baili,
Zhang Yu,
Zhao Lizi,
Zhong Guoping,
Hu Pinjin,
Chen Minhu,
Huang Ming
Publication year - 2012
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 - 10.1002/ibd.21676
Subject(s) - thiopurine methyltransferase , leukopenia , hypoxanthine guanine phosphoribosyltransferase , inflammatory bowel disease , azathioprine , medicine , pharmacology , hypoxanthine phosphoribosyltransferase , toxicity , gastroenterology , chemistry , biochemistry , disease , mutant , gene
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. (Inflamm Bowel Dis 2011;)