Pharmacogenomics Center (PROMISE), Faculty of Pharmacy, Universiti Teknologi MARA, Selangor, Malaysia.
J Clin Pharm Ther. 2012 Apr;37(2):237-41. doi: 10.1111/j.1365-2710.2011.01272.x. Epub 2011 May 5.
Genetic polymorphisms of thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphohydrolase (ITPA 94C>A) contribute to variable responses, including fatal adverse effects, among subjects treated with 6-mercaptopurine (6-MP). Our objectives were to investigate the distribution of specific TPMT and ITPA genotypes in healthy subjects and patients with acute lymphoblastic leukaemia (ALL) from the three main ethnic groups (Malays, Chinese and Indians) in Malaysia and the association of the polymorphisms with adverse effects of 6-MP.
Patients with ALL and healthy controls were recruited and genotyped for genetic variants of TPMT and ITPA 94C>A. The relationship between genotypes and clinical outcomes was investigated.
Acute lymphoblastic leukaemia patients with allele ITPA 94A were more likely to develop fever and liver toxicity with 6-MP. The prevalence of TPMT variants was low and this makes it unlikely that testing for them would be useful in our populations. Only patients heterozygous for TPMT*3C were detected.
Our results suggest that ITPA 94C>A testing, but not TPMT testing, may help in minimizing the adverse effects of 6-MP in Malaysian patients. However, whether this is true in clinical practice requires a larger study and formal randomized controlled evaluation.
巯嘌呤 S-甲基转移酶（TPMT）和肌苷三磷酸焦磷酸水解酶（ITPA94C>A）的遗传多态性导致个体在接受 6-巯基嘌呤（6-MP）治疗时出现不同的反应，包括致命的不良反应。我们的目的是研究特定 TPMT 和 ITPA 基因型在马来西亚三个主要族群（马来人、华人、印度人）的健康受试者和急性淋巴细胞白血病（ALL）患者中的分布，以及这些多态性与 6-MP 不良反应的关系。
招募 ALL 患者和健康对照者进行 TPMT 和 ITPA94C>A 基因变异的基因分型，并研究基因型与临床结局的关系。
携带 ITPA94A 等位基因的 ALL 患者更有可能出现发热和肝功能毒性等不良反应。TPMT 变异的发生率较低，因此在我们的人群中进行检测不太可能有用。仅检测到 TPMT*3C 杂合子的患者。
我们的结果表明，ITPA94C>A 检测，而不是 TPMT 检测，可能有助于减少马来西亚患者 6-MP 的不良反应。然而，这在临床实践中是否正确，需要更大的研究和正式的随机对照评估。
