title: Thiopurine S-methyltransferase gene polymorphism in Japanese patients with autoimmune liver diseases.
abstract: OBJECTIVE
  Thiopurine S-methyltransferase (TPMT) genotypes or phenotypes may be a predictive factor for azathioprine-induced toxicities. We investigated the genotypic status of TPMT to evaluate the risk of azathioprine-related adverse effects in Japanese patients with different liver diseases, including autoimmune hepatitis (AIH).
  
  
  METHODS
  49 patients with AIH, 67 with primary biliary cirrhosis (PBC), and 120 with hepatitis C virus (HCV) were examined. TPMT genotypes were determined by PCR-restriction fragment length polymorphism-based assays.
  
  
  RESULTS
  The distribution of TPMT genotypes was 90% TPMT*1/TPMT*1, 8% TPMT*1/TPMT*3C, and 2% TPMT*3C/TPMT*3C in AIH, and 94% TPMT*1/TPMT*1, 4.5% TPMT*1/TPMT*3C, and 1.5% TPMT*3C/TPMT*3C in PBC. All except 1 patient with HCV had the TPMT*1/TPMT*1 genotype. Severe myelosuppression occurred in two of nine patients with AIH who received azathioprine, one of whom was homozygous for TPMT*3C.
  
  
  CONCLUSIONS
  TPMT*3C variants are more frequent in patients with AIH or PBC than in patients with viral hepatitis or healthy volunteers in Japan. Pharmacogenetic screening for TPMT polymorphisms before commencing azathioprine therapy may help to prevent severe hematotoxicity in patients with TPMT deficiency.
authors.affiliation: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan. atamori@med.osaka-cu.ac.jp
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.forename: Mayumi
authors.initials: M
authors.lastname: Shinzaki
authors.forename: Saori
authors.initials: S
authors.lastname: Kosaka
authors.forename: Takehiro
authors.initials: T
authors.lastname: Hayashi
authors.forename: Shuji
authors.initials: S
authors.lastname: Iwai
authors.forename: Masaru
authors.initials: M
authors.lastname: Enomoto
authors.forename: Daiki
authors.initials: D
authors.lastname: Habu
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
authors.forename: Susumu
authors.initials: S
authors.lastname: Shiomi
authors.forename: Shuhei
authors.initials: S
authors.lastname: Nishiguchi
mesh_terms: D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000139:chemically induced; D044466:Asian People; D001379:Azathioprine / Q000009:adverse effects / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D020022:Genetic Predisposition to Disease; D019693:Hepatitis, Autoimmune / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000378:metabolism; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine