PREVALENCE OF THIOPURINE S-METHYLTRANSFERASE (TPMT) GENE VARIANTS IN THAI PATIENTS SUFFERING TOXICITY FROM THIOGUANINE-CONTAINING CHILDHOOD LEUKEMIA PROTOCOLS: FIRST REPORT OF TPMT*3A IN THAIS

Thiopurine S-methyltransferase (TPMT) is a cytoplasmic enzyme that catalyzes anticancer thiopurine drugs into less active metabolites. As a result, acute leukemia patients with TPMT deficiency will likely be at increased risk for developing toxicity. TPMT activity can be indirectly assessed by genotyping polymorphisms of TPMT, an encoding gene. Since the frequency of TPMT polymorphisms differs by ethnicity, it is important to determine the prevalence of TPMT variants in each ethnic population. The aim of this study was to determine the prevalence of 5 common polymorphisms of TPMT gene in Thai children with acute lymphoblastic leukemia/lymphoblastic lymphoma or acute non-lymphoblastic leukemia who experienced toxicity during treatment regimens that contained thiopurine drugs. A total of 164 patients were evaluated using allele-specific polymerase chain reaction (AS-PCR) for TPMT*2, and PCR-restriction fragment length polymorphism (RFLP) for TPMT*3A, *3B, *3c, and *6 detection. Seven of 164 (4.26%) patients had TPMT variants. Six patients had TPMT*3C/*1 and one patient had TPMT*3A/*1. This is the first report of TPMT*3A polymorphism in Thai population. The percentage frequencies of genotypes TPMT*3C/*1 and TPMT*3A/*1 were 3.65% and 0.61%, respectively. The allele frequencies of TPMT*3C and *3A were 1.82, and 0.30, respectively. Prevalence of the 5 common TPMT variants in Thai children with thiopurine-associated toxicity in this study was low. This finding indicates the necessity of further phamacogenomic study Of other candidate-genes to completely justify the risk of thiopurine-related toxicities in Thai population.