title: Analysis of thiopurine S-methyltransferase genotypes in Japanese patients with inflammatory bowel disease.
abstract: OBJECTIVE
  Myelosuppression observed in patients with inflammatory bowel disease (IBD) treated with azathioprine (AZA) has been attributed to low thiopurine S-methyltransferase (TPMT) activity. TPMT activity is dependent on the genetic polymorphism of high-versus low-metabolizing alleles. We investigated the association between TPMT genotypes and myelosuppression in Japanese IBD patients.
  
  
  METHODS
  Forty-one healthy volunteers and 70 IBD patients (UC, n = 50; CD, n = 20) were recruited. All IBD patients were treated with AZA. The TPMT genotypes were determined by polymerase-chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses.
  
  
  RESULTS
  One healthy volunteer showed a heterozygous mutation of TPMT*1/*3C. All other volunteers and the 70 IBD patients were of the wild alleleotype (TPMT*1/*1). In the IBD patients, 7 patients developed leucopenia (<3,000/microL). One of them developed severe leucopenia (<1,000 microL) with agranulocytosis on day 14 after drug initiation.
  
  
  CONCLUSIONS
  TPMT mutations are not associated with myelosuppression in Japanese IBD patients. Even in IBD patients with a wild TPMT genotype, clinicians should pay attention for the possible development of myelosuppression.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Ban
authors.forename: Akira
authors.initials: A
authors.lastname: Andoh
authors.forename: Aiko
authors.initials: A
authors.lastname: Tanaka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tsujikawa
authors.forename: Masaya
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Saito
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujiyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D003424:Crohn Disease / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D007564:Japan; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D055815:Young Adult
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine