Genetic analysis of thiopurine methyltransferase polymorphism in the 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.


OBJECTIVE
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.


CONCLUSIONS
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.
Faculty of Pharmacy, University of Jordan, Amman 11942, Jordan, nhakooz@ju.edu.jo
Nancy
N
Hakooz
Tawfiq
T
Arafat
Debbie
D
Payne
William
W
Ollier
Sudeep
S
Pushpakom
Julie
J
Andrews
William
W
Newman
D000328:Adult; D018912:Arabs / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007597:Jordan / Q000453:epidemiology; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D044465:White People / Q000235:genetics*
D008780:Methyltransferases; C022745:thiopurine methyltransferase