Thiopurine methyltransferase phenotype and genotype in relation to azathioprine therapy in autoimmune hepatitis

Background/Aims: Toxicity and efficacy of azathioprine is governed partly by the activity of thiopurine methyltransferase (TPMT). Azathioprine has been used for many years, with corticosteroids or alone, for the treatment of autoimmune hepatitis (AIH) but no studies of TPMT phenotype and genotype in...

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Bibliographic Details
Published in:Journal of hepatology 2002-10, Vol.37 (4), p.441-447
Main Authors: Langley, Peter G., Underhill, James, Tredger, J.Michael, Norris, Suzanne, McFarlane, Ian G.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Autoimmune hepatitis
Azathioprine
Azathioprine - administration & dosage
Biological and medical sciences
Erythrocytes - enzymology
Female
Genotype
Hepatitis, Autoimmune - drug therapy
Hepatitis, Autoimmune - genetics
Hepatitis, Autoimmune - metabolism
Humans
Immunomodulators
Immunosuppressive Agents - administration & dosage
Male
Medical sciences
Methyltransferases - genetics
Middle Aged
Pharmacology. Drug treatments
Phenotype
Polymorphism, Genetic
Thiopurine methyltransferase
Treatment Outcome
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Summary:Background/Aims: Toxicity and efficacy of azathioprine is governed partly by the activity of thiopurine methyltransferase (TPMT). Azathioprine has been used for many years, with corticosteroids or alone, for the treatment of autoimmune hepatitis (AIH) but no studies of TPMT phenotype and genotype in relation to response to the drug in AIH have been published. Methods: Erythrocyte TPMT activities were measured by a radioincorporation assay in 72 consecutive outpatients with AIH, 53 of whom were genotyped for the commonest defective alleles in Europeans ( TPMT*3A, *3B and *3C) by restriction fragment length polymorphism analysis. Results: TPMT activities were significantly lower in patients intolerant of azathioprine (group I, n=15) than in those who sustained remission on azathioprine alone (group II, n=28; P=0.003) and those who tolerated azathioprine but continued to require corticosteroids (group III, n=29; P
ISSN:0168-8278
1600-0641
DOI:10.1016/S0168-8278(02)00214-3