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 TPMT∗2 and TPMT∗3. 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. TPMT∗3C was found in 25 patients (2.8%): 24 patients with TPMT∗1/∗3 and one with TPMT∗3/∗3. Rare TPMT variants including TPMT∗6, TPMT∗16, and TPMT∗32 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.