Thiopurine S-methyltransferase gene polymorphism in Japanese patients with autoimmune liver diseases
| Autor: | Shuhei Nishiguchi, Hiroki Sakaguchi, Takehiro Hayashi, Mayumi Shinzaki, Akihiro Tamori, Masayuki Hino, Susumu Shiomi, Saori Kosaka, Masaru Enomoto, Shuji Iwai, Norifumi Kawada, Daiki Habu |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Gastrointestinal Diseases Hepatitis C virus Azathioprine Autoimmune hepatitis Pharmacology medicine.disease_cause Gastroenterology Thiopurine S-Methyltransferase Primary biliary cirrhosis Asian People Bone Marrow Internal medicine medicine Humans Genetic Predisposition to Disease Aged Polymorphism Genetic Hepatology Thiopurine methyltransferase biology business.industry Methyltransferases Middle Aged medicine.disease Thrombocytopenia digestive system diseases Hepatitis Autoimmune biology.protein Female business Viral hepatitis Pharmacogenetics Immunosuppressive Agents medicine.drug Agranulocytosis |
| Zdroj: | Liver international : official journal of the International Association for the Study of the Liver. 27(1) |
| ISSN: | 1478-3223 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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