Laróvere L E, de Kremer R Dodelson, Lambooy L H J, De Abreu R A
Centro de Estudio de las Metabolopatías l Congénitas, Cátedra de Clínica Pediátrica l Universidad Nacional de Córdoba Hospital de Niños de la Santísima Trinidad l Ferroviarios 1250, X5014AKN Córdoba, Argentina.
Ann Clin Biochem. 2003 Jul;40(Pt 4):388-93. doi: 10.1258/000456303766477039.
Thiopurine methyltransferase (TPMT) catalyses the S-methylation of 6-thiopurine drugs, which are commonly used in the treatment of autoimmune diseases, leukaemia and organ transplantation. TPMT activity is polymorphic as a result of gene mutations. Ethnic variations in phenotype and genotype have been identified in previous population studies, but no information was available within Latin-American populations.
To establish the genetic polymorphism of TPMT in an Argentine population.
TPMT enzymatic activity of 147 healthy Argentine subjects was measured using a high-performance liquid chromatography method. The genotyping assay for nine defective alleles (TPMT*2 - *8) was based on restriction fragment length polymorphism polymerase chain reaction and allele-specific polymerase chain reaction methods.
All subjects had detectable TPMT activity. Twelve individuals with low to intermediate activity were heterozygous for one of the mutant alleles: nine were TPMT*1/3A, two TPMT1/2 and one TPMT1/4. All examined subjects with normal activity had wild-type genotype (TPMT1/*1).
Variant TPMT alleles were present in 8.2% of the examined subjects, which is in accordance with other studies. The frequency of TPMT3A, TPMT2 and TPMT4 was 3.1%, 0.7% and 0.3%, respectively. TPMT3A was the most prevalent allele, which is in accordance with results from Caucasian populations. This study provides the first analysis of TPMT activity and allele frequency distribution in Argentina, South America.
硫嘌呤甲基转移酶（TPMT）催化6-硫嘌呤类药物的S-甲基化反应，这类药物常用于治疗自身免疫性疾病、白血病和器官移植。由于基因突变，TPMT活性具有多态性。以往的人群研究已发现表型和基因型存在种族差异，但拉丁美洲人群中尚无相关信息。
确定阿根廷人群中TPMT的基因多态性。
采用高效液相色谱法测定147名健康阿根廷受试者的TPMT酶活性。针对9个缺陷等位基因（TPMT*2 - *8）的基因分型检测基于限制性片段长度多态性聚合酶链反应和等位基因特异性聚合酶链反应方法。
所有受试者均可检测到TPMT活性。12名活性低至中等的个体为其中一种突变等位基因的杂合子：9名为TPMT*1/3A，2名为TPMT1/2，1名为TPMT1/4。所有活性正常的受试对象均具有野生型基因型（TPMT1/*1）。
8.2%的受试对象存在TPMT变异等位基因，这与其他研究结果一致。TPMT3A、TPMT2和TPMT4的频率分别为3.1%、0.7%和0.3%。TPMT3A是最常见的等位基因，这与白种人群的结果一致。本研究首次分析了南美洲阿根廷人群中TPMT的活性和等位基因频率分布。
