Complete sequence-based screening of TPMT variants in the Korean population.

Thiopurine S-methyltransferase (TPMT) is a cytoplasmic enzyme involved in the metabolism of thiopurine drugs and its activity is largely influenced by polymorphisms of the TPMT gene. To date, more than 35 TPMT variants are known to be associated with reduced enzyme activity, but most studies on the TPMT genotype have included only common nonfunctional variants, such as TPMT2 and TPMT3. In this study, we carried out a complete sequencing analysis to screen all TPMT variants in Korean patients. A total of 900 Korean patients were genotyped for TPMT and 30 patients (3.3%) had the known TPMT variant alleles. TPMT3C was found in 25 patients (2.8%): 24 patients with TPMT1/3 and one with TPMT3/3. Rare TPMT variants including TPMT6, TPMT16, and TPMT32 were detected in five patients (0.6%) and a novel variant, TPMT*38 (c.514T>C, p.S172P), was identified in two patients. This is the first complete sequence-based screening study evaluating all TPMT variants in Asian populations.