Zhang Jian-Ping, Zhou Shu-Feng, Chen Xiao, Huang Min
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, China.
Clin Chim Acta. 2006 Mar;365(1-2):337-41. doi: 10.1016/j.cca.2005.09.005. Epub 2005 Oct 11.
Thiopurine S-methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. Several mutations in the TPMT gene have been identified which correlate with a low activity phenotype. The molecular basis for TPMT deficiency is not well defined in minority Chinese. We investigated differences in the activity of TPMT and the frequencies of mutant TPMT alleles in 4 ethnic groups of Chinese.
The frequency of 4 common TPMT mutant alleles, TPMT2, TPMT3A, TPMT3B and TPMT3C, were determined in healthy subjects from Han (n=312), Jing (n=103), Yao (n=126) and Uygur Chinese (n=160) by allele-specific PCR and PCR-restriction RFLP analysis. TPMT activity in erythrocytes was determined by HPLC.
There was no significant difference in the mean TPMT activity between all ethnic groups studied and no subject with TPMT deficiency was found in all populations studied. TPMT3C was found in 2.2% of Han and 1.9% of Jing Chinese. TPMT2, TPMT3B and TPMT3A alleles were not detected in any of the Han or Jing Chinese tested. In contrast, 3.7% of Uygur Chinese had TPMT3C and TPMT3A alleles. Neither allele was detected in Yao Chinese. The overall frequencies of variant TPMT allele in Uygur were higher than in Han or Jing Chinese. However, neither the overall frequency of mutant TPMT alleles nor the genotype frequencies were significantly different between Han, Jing, Yao and Uygur Chinese.
The TPMT3C was the most prevalent allele in Han, Jing and Uygur Chinese, while TPMT3A is a rare allele in Uygur Chinese who belong to Caucasian. Ethnicity may be an important factor affecting the variability in response to thiopurine chemotherapy.
硫嘌呤S-甲基转移酶（TPMT）催化硫嘌呤类药物的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。中国少数民族中TPMT缺乏的分子基础尚不明确。我们调查了中国4个民族中TPMT活性的差异以及突变TPMT等位基因的频率。
采用等位基因特异性PCR和PCR-限制性片段长度多态性分析，对汉族（n = 312）、京族（n = 103）、瑶族（n = 126）和维吾尔族（n = 160）健康受试者中4种常见TPMT突变等位基因TPMT2、TPMT3A、TPMT3B和TPMT3C的频率进行测定。通过高效液相色谱法测定红细胞中的TPMT活性。
在所研究的所有民族中，平均TPMT活性无显著差异，且在所有研究人群中均未发现TPMT缺乏的个体。汉族中2.2%、京族中1.9%的个体检测到TPMT3C。在所检测的汉族或京族个体中均未检测到TPMT2、TPMT3B和TPMT3A等位基因。相比之下，3.7%的维吾尔族个体检测到TPMT3C和TPMT3A等位基因。瑶族个体中未检测到这两种等位基因。维吾尔族中TPMT变异等位基因的总体频率高于汉族或京族。然而，汉族、京族、瑶族和维吾尔族之间TPMT突变等位基因的总体频率和基因型频率均无显著差异。
TPMT3C是汉族、京族和维吾尔族中最常见的等位基因，而TPMT3A在属于高加索人种的维吾尔族中是罕见等位基因。种族可能是影响硫嘌呤化疗反应变异性的重要因素。
