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- Title
Adverse reactions to azathioprine cannot be predicted by thiopurine S-methyltransferase genotype in Japanese patients with inflammatory bowel disease.
- Authors
Takatsu, Noritaka; Matsui, Toshiyuki; Murakami, Yuji; Ishihara, Hiroshi; Hisabe, Takashi; Nagahama, Takashi; Maki, Shinichirou; Beppu, Takahiro; Takaki, Yasuhiro; Hirai, Fumihito; Yao, Kenshi
- Abstract
Background and Aims: Azathioprine (AZA) is associated with a high frequency of adverse reactions. We examined polymorphism of the thiopurine S-methyltransferase (TPMT) gene to determine whether the TPMT genotype would be a predictive marker for the development of adverse reactions to AZA. Methods: The frequency of TPMT mutations was investigated in 147 Japanese inflammatory bowel disease (IBD) patients retrospectively. In these subjects, the presence of four mutant alleles (TPMT*2, *3B, *3C and *8) was determined by direct sequencing. The incidence of adverse reactions among patients carrying wild-type TPMT was investigated. The blood level of 6-thioguanine nucleotide (6-TGN) was measured and analyzed in 47 patients with wild-type TPMT. The results were analyzed in relation to the concomitant use of aminosalicylates (ASA). Results: Of the 147 patients, 144 (98.0%) were wild-type for TPMT (TPMT*1/*1) and three (2.0%) carried a mutant TPMT allele (TPMT*1/*3C). The incidence of adverse reactions was 33.3% (38/114) in the wild-type group. Leukopenia (WBC ≤ 3000/µL) was seen in 15.8% of the patients with wild-type TPMT. 6-TGN levels varied among 47 patients with wild-type TPMT. The blood levels of 6-TGN were significantly higher in the patients receiving concomitant ASA treatment compared with those not receiving concomitant ASA treatment ( P = 0.0033). Conclusion: The frequency of TPMT gene mutations is low among Japanese IBD patients. The incidence of adverse reactions to AZA was high, even in patients carrying wild-type TPMT. It is concluded that determination of TPMT genotype may not be useful in Japanese IBD patients to predict adverse reactions to AZA.
- Subjects
DRUG side effects; PHARMACODYNAMICS; IMMUNOSUPPRESSIVE agents; INFLAMMATORY bowel diseases; INTESTINAL diseases; GASTROENTEROLOGY; JAPANESE people; DISEASES
- Publication
Journal of Gastroenterology & Hepatology, 2009, Vol 24, Issue 7, p1258
- ISSN
0815-9319
- Publication type
Article
- DOI
10.1111/j.1440-1746.2009.05917.x