Literature DB >> 20521035

Genetic analysis of thiopurine methyltransferase polymorphism in the Jordanian population.

Nancy Hakooz1, Tawfiq Arafat, Debbie Payne, William Ollier, Sudeep Pushpakom, Julie Andrews, William Newman.   

Abstract

UNLABELLED: This study provides the first analysis of the TPMT mutant allele frequency in a sample of the Jordanian population and indicates that TPMT*3A is the most common allele in Jordanian subjects.
PURPOSE: thiopurine methyltransferase TPMT catalyses the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathiopurine. Thiopurine methyltransferase (TPMT) polymorphisms are the major determinants of interindividual differences in the severe haematological toxicity of 6-mercaptopurine. Several variants in the TPMT gene have been identified that correlate with a low activity phenotype. Four variant alleles, TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C, are responsible for over 80% of the low or undetectable enzyme activity. The allelic frequency of TPMT variants has been established in many populations.
METHODS: In this study, the frequencies of four (TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C) variants were investigated in 169 healthy Jordanian men (18-45 years of age). Single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassARRAY technology (Sequenom; San Diego, CA, USA).
RESULTS: TPMT*3A and TPMT*3C were the only deficiency alleles detected in the Jordanian population with an allele frequency of 0.59% and 0.30% respectively. The TPMT*3A allele frequency is found to be lower than in the European Caucasian population.
CONCLUSION: TPMT*3A and TPMT*3C were the only deficiency alleles detected in the Jordanian population with an allele frequency of 0.59% and 0.30% respectively. The TPMT*3A allele frequency is found to be lower than in the European Caucasian population.

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Year:  2010        PMID: 20521035     DOI: 10.1007/s00228-010-0826-1

Source DB:  PubMed          Journal:  Eur J Clin Pharmacol        ISSN: 0031-6970            Impact factor:   2.953


  32 in total

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10.  ITPA, TPMT, and NUDT15 Genetic Polymorphisms Predict 6-Mercaptopurine Toxicity in Middle Eastern Children With Acute Lymphoblastic Leukemia.

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