Kim Hyun-Young, Lee Soo Hyun, Lee Mi-Na, Kim Jong-Won, Kim Young-Ho, Kim Mi Jin, Lee Yoo Min, Kang Ben, Choe Yon Ho, Lee Na Hee, Kim Dong Hwan, Yoo Keon Hee, Sung Ki Woong, Lee Soo-Youn, Koo Hong Hoe
Departments of aLaboratory Medicine and Genetics bPediatrics cInternal Medicine dClinical Pharmacology and Therapeutics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Pharmacogenet Genomics. 2015 Mar;25(3):143-6. doi: 10.1097/FPC.0000000000000117.
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.
硫嘌呤甲基转移酶（TPMT）是一种参与硫嘌呤类药物代谢的胞质酶，其活性在很大程度上受TPMT基因多态性的影响。迄今为止，已知有超过35种TPMT变体与酶活性降低有关，但大多数关于TPMT基因型的研究仅包括常见的无功能变体，如TPMT2和TPMT3。在本研究中，我们进行了全面的测序分析，以筛查韩国患者中的所有TPMT变体。对总共900名韩国患者进行了TPMT基因分型，其中30名患者（3.3%）携带已知的TPMT变体等位基因。在25名患者（2.8%）中发现了TPMT3C：24名患者为TPMT1/3，1名患者为TPMT3/3。在5名患者（0.6%）中检测到包括TPMT6、TPMT16和TPMT32在内的罕见TPMT变体，在2名患者中鉴定出一种新变体TPMT*38（c.514T>C，p.S172P）。这是第一项基于完整序列的筛查研究，评估了亚洲人群中的所有TPMT变体。
