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Genetic polymorphism of Thiopurine S-methyltransferase (TPMT) is a
cytosolic enzyme that preferentially catalyzes the S-methylation of thiopurine drugs
including azathioprine, 6-mercaptopurine and thioguanine. TPMT activity exhibits
autosomal codominant genetic polymorphism and patient inheriting TPMT deficiency
are at high risk of potentially fatal hematopoietic toxicity. To date, more than eight
mutant alleles have been reported, with TPMT*2, TPMT*3A and TPMT*3C being
the most common mutant alleles. These variant alleles results from point mutations in
the TPMT open reading frame leading to decrease in enzymatic activity. Ethnic
differences in the frequency of mutant alleles are now recognized. TPMT*3A is the
most prevalent mutant allele in Caucasians, with TPMT*3C and TPMT*2 being rare
allele whereas TPMT*3C is the most prevalent mutant allele in East Asians. The
aims of the present study were to elucidate the genetic basis for the TPMT
polymorphism in a Northeastern Thai population. TPMT*1 to TPMT*3 were
analyzed using the polymerase chain reaction-restriction fragment length
polymorphism (PCR-RFLP) and allele specific PCR. Among the 200 Northeastern
healthy Thai subjects genotyped, 181 subjects (90.5%) were homozygous wild type
allele (TPMT*1/TPMT*1), 18 subjects (9.0%) were heterozygotes (TPMT*1/
TPMT*3C) and 1 subject (0.5%) was homozygous mutant (TPMT*3C/ TPMT*3C).
Only TPMT*3C variant allele was found in this population and the frequency of this
mutant allele accounts for 5%. This study confirms ethnic differences in TPMT allele
frequency and about 9.5% of a Northeastern Thai population have an increased risk
for thiopurine-induced toxicity.
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