Thiopurine S-Methyltransferase (TPMT) Gene Polymorphism in Brazilian Children With Acute Lymphoblastic Leukemia: Association With Clinical and Laboratory Data
Thiopurine S-Methyltransferase (TPMT) Gene Polymorphism in Brazilian Children With Acute Lymphoblastic Leukemia: Association With Clinical and Laboratory Data
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DOI：
10.1097/ftd.0b013e31818b0f31
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发表时间：
2008-12-01
影响因子：
2.5
通讯作者：
Romanha, Alvaro Jose
中科院分区：
文献类型：
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作者：
Silva, Marcilene Rezende;de Oliveira, Benigna Maria;Romanha, Alvaro Jose
在116名患有急性淋巴细胞白血病的巴西儿童中，对TPMT*2、*3A、*3B和*3C等位基因变异的频率进行了估计。分析基因分型与化疗维持期临床和实验室指标的关系，以及红细胞内6-硫鸟嘌呤代谢产物(6-硫鸟嘌呤核苷酸和甲硫基嘌呤)浓度的相关性。DNA扩增采用多重扩增难扩增体系-聚合酶链式反应(ARMS-PCR)。12例患者存在TPMT基因突变，均为杂合子形式。最常见的等位基因变异是TPMT*3A(3.9%)，其次是*3C(0.9%)、*2(0.4%)和*3B(0%)。临床和实验室数据与TPMT基因突变的存在没有显著关联。在接受6-巯基嘌呤代谢物水平监测的36名患者中，只有1人发生了突变。在这例患者中，发现高6-硫鸟嘌呤核苷酸和低甲硫基嘌呤浓度。全组无事件生存率(EFS)为73.4%。突变组与无突变组的无事件生存率比较，差异无统计学意义(P=0.06)。
The frequency of allele variants of gene TPMT*2, *3A, *3B, and *3C was estimated in a population of 116 Brazilian children with acute lymphoblastic leukemia. The association between genotype and clinical and laboratory data obtained during chemotherapy maintenance phase and the correlation of intraerythrocyte concentration of 6-mercaptopurine metabolites (6-tioguanine nucleotide nucleotides and methylmercaptopurine) were analyzed. A multiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was used in DNA amplification. Twelve patients presented TPMT gene mutation, all in heterozygous form. The most frequent allele variation was TPMT*3A (3.9%), followed by *3C (0.9%), *2 (0.4%), and *3B (0%). There was no significant association between clinical and laboratory data and the presence of mutation in TPMT gene. Of the 36 patients who were monitored for 6-mercaptopurine metabolite levels, only 1 had the mutation. In this patient, high 6-tioguanine nucleotide and low methylmercaptopurine concentrations were found. Event-free Survival (EFS) for the whole group was 73.4%. There was no significant difference in event-free survival in the comparison between the groups with and without mutation (P = 0.06).