Premium
Thiopurine S‐methyltransferase gene polymorphism in Japanese patients with autoimmune liver diseases
Author(s) -
Tamori Akihiro,
Shinzaki Mayumi,
Kosaka Saori,
Hayashi Takehiro,
Iwai Shuji,
Enomoto Masaru,
Habu Daiki,
Sakaguchi Hiroki,
Kawada Norifumi,
Hino Masayuki,
Shiomi Susumu,
Nishiguchi Shuhei
Publication year - 2007
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2006.01392.x
Subject(s) - thiopurine methyltransferase , azathioprine , autoimmune hepatitis , medicine , genotype , pharmacogenetics , cirrhosis , hepatitis , gastroenterology , immunology , biology , gene , genetics , disease
Background and aim: 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.