Genetic analysis of thiopurine methyltransferase polymorphism in the Jordanian population

作者：Hakooz Nancy^*; Arafat Tawfiq; Payne Debbie; Ollier William; Pushpakom Sudeep; Andrews Julie; Newman William

来源：European Journal of Clinical Pharmacology, 2010, 66(10): 999-1003.

DOI：10.1007/s00228-010-0826-1

• TPMT
• Genotyping
• Jordanian population

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.
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.
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 SequenomA (R) MassARRAY technology (SequenomA (R); San Diego, CA, USA).
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.
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.

• 出版日期2010-10