Genetic analysis of thiopurine methyltransferase polymorphism in the Jordanian population.

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, TPMT2, TPMT3A, TPMT3B and TPMT3C, 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 (TPMT2, TPMT3A, TPMT3B and TPMT3C) 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

TPMT3A and TPMT3C 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

TPMT3A and TPMT3C 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.