Lu H-F, Shih M-C, Hsueh S-C, Chen C-M, Chang J-Y, Chang J-G
Department of Molecular Medicine, China Medical University Hospital, Taichung, China.
J Clin Pharm Ther. 2005 Oct;30(5):491-6. doi: 10.1111/j.1365-2710.2005.00640_1.x.
Thiopurine drugs are used as immunosuppressant or cytotoxic drugs. Thiopurine S-methyltransferase (TPMT) methylates and thereby modulates the therapeutic and toxic effects of these drugs. The activity of TPMT is affected by genetic polymorphism of TPMT alleles, and these alleles have not been studied in Tibetans and Bolivians.
To analyse the TPMT allelic frequencies in Tibetans and Bolivians.
We developed an inexpensive method for collecting blood and extracting genomic DNA. Genomic DNA was extracted from blood spots of 50 Tibetans and 115 Bolivians. The frequencies of allelic variants of TPMT gene (TPMT1 to TPMT8) were determined using polymerase chain reaction-restriction fragment length polymorphism technique.
The allelic frequencies of TPMT1 were 99 and 93.48% for Tibetans and Bolivians, respectively. The corresponding allelic frequencies of TPMT3A were 0 and 6.52% and those of TPMT3C were 1.0 and 0%. No TPMT2, 3B, 3D, 4-8 were found in these two populations.
As with Caucasian populations, TPMT*3A is the most prevalent mutant allele in Bolivians. Our results may be of value in helping to guide the prescription of thiopurine drugs in these populations.
硫嘌呤类药物用作免疫抑制剂或细胞毒性药物。硫嘌呤S-甲基转移酶（TPMT）使这些药物甲基化，从而调节其治疗效果和毒性作用。TPMT的活性受TPMT等位基因的基因多态性影响，而这些等位基因在藏族人和玻利维亚人中尚未得到研究。
分析藏族人和玻利维亚人中TPMT等位基因频率。
我们开发了一种廉价的采血和提取基因组DNA的方法。从50名藏族人和115名玻利维亚人的血斑中提取基因组DNA。使用聚合酶链反应-限制性片段长度多态性技术测定TPMT基因（TPMT1至TPMT8）等位基因变体的频率。
藏族人和玻利维亚人中TPMT1的等位基因频率分别为99%和93.48%。TPMT3A的相应等位基因频率分别为0和6.52%，TPMT3C的相应等位基因频率分别为1.0%和0%。在这两个人群中未发现TPMT2、3B、3D、4 - 8。
与白种人群一样，TPMT*3A是玻利维亚人中最常见的突变等位基因。我们的结果可能有助于指导这些人群中硫嘌呤类药物的处方。
