Molecular Biology Laboratory, Genetics Department, Instituto Nacional de Pediatría, DF, México.
J Clin Pharm Ther. 2009 Dec;34(6):703-8. doi: 10.1111/j.1365-2710.2009.01058.x.
Thiopurine S-methyltransferase (TPMT) is involved in the toxicity and therapeutic efficacy of thiopurine drugs, and its gene exhibits genetic polymorphisms that differ across diverse populations. Four TPMT polymorphisms (TPMT*2, *3A, *3B and *3C) account for 80-95% of alleles that cause reduced enzyme activity. To date, only a single study in the Mexican population involving 108 individuals has been performed, but the regional and ethnic origin of this population was not described. Accordingly, information about the TPMT polymorphism in the Mexican population is limited.
To determine the TPMT allele and genotype frequencies in a sample of newborns from Mexico City.
Three hundred and sixty DNA samples from unrelated, anonymous individuals were obtained from dried blood spots collected on filter paper as part of the Newborn Screening National Program. Allele-specific polymerase chain reaction for the TPMT2 allele and PCR restriction fragment length polymorphism for TPMT3A, TPMT3B, TPMT3C alleles were used to determine the respective allelic and genotypic frequencies.
Of 720 TPMT alleles analysed, 49 (6.81%) were deficiency alleles. The most common deficiency allele was TPMT3A (5.69%), followed by TPMT3C (0.56%), TPMT3B (0.28%) and TPMT2 (0.28%). Fourty-five newborns were heterozygous for one mutant allele (12.5%) and two showed a genotype with two deficiency alleles (0.56%). Despite its unique ethnic composition, our Mexican population exhibited variant allele frequencies that were similar to some Caucasian populations.
Our data suggest that approximately 1 in 180 persons born in Mexico City might have low or undetectable TPMT enzyme activity, a frequency that, overall, is somewhat higher than that reported for Caucasian populations generally (1 in 300).
硫嘌呤甲基转移酶（TPMT）参与硫嘌呤类药物的毒性和治疗效果，其基因存在遗传多态性，在不同人群中存在差异。四种 TPMT 多态性（TPMT*2、*3A、3B 和3C）占导致酶活性降低的等位基因的 80-95%。迄今为止，仅在涉及 108 人的墨西哥人群中进行了一项单一研究，但该人群的区域和种族来源未予描述。因此，有关墨西哥人群 TPMT 多态性的信息有限。
确定墨西哥城新生儿样本中 TPMT 等位基因和基因型频率。
从作为新生儿筛查国家计划一部分收集的滤纸干血斑中获得 360 个无关匿名个体的 DNA 样本。使用 TPMT2 等位基因的等位基因特异性聚合酶链反应和 TPMT3A、TPMT3B、TPMT3C 等位基因的 PCR 限制性片段长度多态性，确定各自的等位基因和基因型频率。
在分析的 720 个 TPMT 等位基因中，有 49 个（6.81%）为缺陷等位基因。最常见的缺陷等位基因是 TPMT3A（5.69%），其次是 TPMT3C（0.56%）、TPMT3B（0.28%）和 TPMT2（0.28%）。45 名新生儿为一个突变等位基因的杂合子（12.5%），两名新生儿显示出两种缺陷等位基因的基因型（0.56%）。尽管其具有独特的种族构成，但我们的墨西哥人群的变异等位基因频率与一些白种人群相似。
我们的数据表明，在墨西哥城出生的人中，大约每 180 人就有 1 人可能具有低或无法检测到的 TPMT 酶活性，这一频率总体上略高于一般白种人群（每 300 人中有 1 人）。
