Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia.
Prevalence of TPMT and ITPA gene polymorphisms and effect on mercaptopurine dosage in Chilean children with acute lymphoblastic leukemia.
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DOI：
10.1186/1471-2407-14-299
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发表时间：
2014-04-28
期刊：
影响因子：
3.8
通讯作者：
Morales J
中科院分区：
文献类型：
--
作者：
Farfan MJ;Salas C;Canales C;Silva F;Villarroel M;Kopp K;Torres JP;Santolaya ME;Morales J
巯基嘌呤（6-MP）在儿童急性淋巴细胞白血病（ALL）的治疗中起着关键作用;然而，由于6-MP代谢酶的遗传多态性，该药物的毒性存在个体间差异。我们确定了智利ALL儿童6-MP代谢酶主要遗传多态性的患病率。入组了103例确诊为ALL的智利儿科患者。从全血中提取DNA，采用聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）检测硫嘌呤甲基转移酶（TPMT）和三磷酸肌苷焦磷酸酶（ITPA）编码基因的遗传多态性。TPMT等位基因变异总频率为8%。TPMT*2、TPMT*3A和TPMT*3B等位基因的检出率分别为0%、7%和1%。ITPA中P32 T等位基因频率为3%。我们没有观察到任何TPMT和ITPA等位基因的纯合子变异。我们还分析了一个亚组的40例患者完成了维持阶段的ALL治疗，我们发现，携带TPMT基因变异等位基因的患者需要显着较低的中位累积剂量和中位日剂量的6-MP比携带野生型等位基因的患者。TMPT基因分型似乎是进一步优化智利ALL患者6-MP治疗设计的重要工具。
Mercaptopurine (6-MP) plays a pivotal role in treatment of childhood acute lymphoblastic leukemia (ALL); however, interindividual variability in toxicity of this drug due to genetic polymorphism in 6-MP metabolizing enzymes has been described. We determined the prevalence of the major genetic polymorphisms in 6-MP metabolizing enzymes in Chilean children with ALL. 103 Chilean pediatric patients with a confirmed diagnosis of ALL were enrolled. DNA was isolated from whole blood and genetic polymorphism in thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) coding genes were detected by polymorphism chain reaction-restriction fragment length (PCR-RFLP) assay. The total frequency of variant TPMT alleles was 8%. TPMT*2, TPMT*3A and TPMT*3B alleles were found in 0%, 7%, and 1% of patients, respectively. For ITPA, the frequency of P32T allele was 3%. We did not observe any homozygous variant for TPMT and ITPA alleles. We also analyzed a subgroup of 40 patients who completed the maintenance phase of ALL treatment, and we found that patients carrying a TPMT gene variant allele required a significantly lower median cumulative dosage and median daily dosage of 6-MP than patients carrying wild type alleles. TMPT genotyping appears an important tool to further optimize 6-MP treatment design in Chilean patients with ALL.
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影响因子：
45.3
作者：
Evans, WE;Hon, YY;Relling, MV
通讯作者：
Relling, MV
影响因子：
3.2
作者：
Peregud-Pogorzelski, Jaroslaw;Tetera-Rudnicka, Edyta;Drozdzik, Marek
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Drozdzik, Marek
影响因子：
2.8
作者：
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De Marco, L
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2.5
作者：
Silva, Marcilene Rezende;de Oliveira, Benigna Maria;Romanha, Alvaro Jose
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Romanha, Alvaro Jose
影响因子：
39.2
作者：
Yates, CR;Krynetski, EY;Evans, WE
通讯作者：
Evans, WE