Hiratsuka M, Inoue T, Omori F, Agatsuma Y, Mizugaki M
Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Mutat Res. 2000 Mar 14;448(1):91-5. doi: 10.1016/s0027-5107(00)00004-x.
Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathiopurine. Several mutations in the TPMT gene have been identified which correlate with a low activity phenotype. The molecular basis for the genetic polymorphism of TPMT has been established for European Caucasians, African-Americans, Southwest Asians and Chinese, but it remains to be elucidated in Japanese populations. The frequency of the four allelic variants of the TPMT gene, TPMT2 (G238C), TPMT3A (G460A and A719G), TPMT3B (G460A) and TPMT3C (A719G) were determined in Japanese samples (n=192) using polymerase chain reaction (PCR)-RFLP and allele-specific PCR-based assays. TPMT3C was found in 0.8% of the samples (three heterozygotes). The TPMT2, TPMT3A and TPMT3B alleles were not detected in any of the samples analyzed. This study provides the first analysis of TPMT mutant allele frequency in a sample of Japanese population and indicates that TPMT*3C is the most common allele in Japanese subjects.
硫嘌呤甲基转移酶（TPMT）催化硫嘌呤类药物（如6-巯基嘌呤、6-硫鸟嘌呤和硫唑嘌呤）的S-甲基化反应。已鉴定出TPMT基因中的几种突变，这些突变与低活性表型相关。欧洲白种人、非裔美国人、西南亚人和中国人的TPMT基因多态性的分子基础已经明确，但在日本人群中仍有待阐明。使用聚合酶链反应（PCR）-限制性片段长度多态性分析（RFLP）和基于等位基因特异性PCR的检测方法，对日本样本（n = 192）中TPMT基因的四种等位基因变体TPMT2（G238C）、TPMT3A（G460A和A719G）、TPMT3B（G460A）和TPMT3C（A719G）的频率进行了测定。在0.8%的样本（三名杂合子）中发现了TPMT3C。在所分析的任何样本中均未检测到TPMT2、TPMT3A和TPMT3B等位基因。本研究首次对日本人群样本中的TPMT突变等位基因频率进行了分析，表明TPMT*3C是日本受试者中最常见的等位基因。
