TPMT genotyping and azathioprine metabolite measurement in patients with auto-immune hepatitis and transplanted kidney.

Nasser, Paulo D., Pacheco-Neto, Maurilio, Cancado, Eduardo L. R., Duley, John A., Chocair, Pedro R., Ferreira, Camila S., Alves, Atecla N. L., Fortin, Alexandre S., Carrilho, Flair Jose and Ono-Nita, Suzane K. (2012). TPMT genotyping and azathioprine metabolite measurement in patients with auto-immune hepatitis and transplanted kidney.. In: III International Thiopurine Symposium, Hospital Alemao Oswaldo Cruz, São Paulo, Brazil, (S45-S45). Sep 30 - Oct 2, 2010.


Author Nasser, Paulo D.
Pacheco-Neto, Maurilio
Cancado, Eduardo L. R.
Duley, John A.
Chocair, Pedro R.
Ferreira, Camila S.
Alves, Atecla N. L.
Fortin, Alexandre S.
Carrilho, Flair Jose
Ono-Nita, Suzane K.
Title of paper TPMT genotyping and azathioprine metabolite measurement in patients with auto-immune hepatitis and transplanted kidney.
Conference name III International Thiopurine Symposium
Conference location Hospital Alemao Oswaldo Cruz, São Paulo, Brazil
Conference dates Sep 30 - Oct 2, 2010
Journal name Associacao Medica Brasileira. Revista   Check publisher's open access policy
Place of Publication Rev Assoc Med Bras.
Publisher Brazilian Medical Association
Publication Year 2012
Sub-type Published abstract
Open Access Status Link (no DOI)
ISSN 0104-4230
Volume 58
Issue Suppl 1
Start page S45
End page S45
Total pages 1
Language eng
Formatted Abstract/Summary
Background: Thiopurine drugs such as azathioprine (AZA) are widely used for many types of treatment: autoimmune and inflammatory diseases as well as organ transplant recipients. AZA is capable of causing adverse effects, with hepatotoxicity and myelosuppression being the most often observed. Thiopurine S-methyltransferase (TPMT), which catalyzes the S-methylation of these drugs, exhibits a genetic polymorphism in 10% of Caucasians, and 1/300 individuals with complete deficiency. Patients with intermediary or complete TPMT activity deficiency are at risk for excessive toxicity after receiving standard doses of thiopurine drugs. Objectives: 1) To investigate the frequency of polymorphisms (TPMT * 2, TPMT * 3A and TPMT * 3C) in blood donors and in patients using azathioprine for the treatment of auto-immune hepatitis and after kidney transplant from a tertiary University Hospital (HCFMUSP), São Paulo, Brazil 2) To compare the levels of AZA metabolite 6-thioguanine (6-TGN) in patients on long-term use of AZA with the genotypes. Materials and methods: 89 autoimmune hepatitis patients, 73 who had undergone kidney transplant, receiving azathioprine, were analyzed as well as a total of 135 blood donors. TPMT mutations were detected by multiplex PCR-ARMS. To confirm the mutant genotypes, TMPT gene was sequenced by ABI-3100 Sequencing System (Applied Biosystem – Foster City, CA). The metabolite (6-TGN) of azathioprine was quantified by HPLC system. Results: The frequency of mutant genotypes was 10.7% in blood donors. The predominant genotype *1/*3A is probably due to the influence of Caucasian ascendancy in the Brazilian population. There were 8.9% and 6.1% heterozygous mutant genotypes (*1/*2, *1/*3A, *1/*3C) in auto-immune patients and patients submitted to kidney transplant, respectively. 6-TGN levels were higher in patients with mutant genotypes in groups with auto-immune hepatitis and transplanted kidney patients. Conclusions: These findings may explain the beneficial effects of azathioprine and have important implications for the design of new targeted therapies in auto-immune diseases and organ transplant.
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Conference Paper
Collection: School of Pharmacy Publications
 
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Created: Fri, 20 Apr 2012, 17:56:59 EST by Dr John Duley on behalf of School of Pharmacy