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首页> 外文期刊>Journal of Clinical and Diagnostic Research >Thiopurine S-Methyltransferase Polymorphism in Iraqi Paediatric Patients with Acute Lymphoblastic Leukaemia
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Thiopurine S-Methyltransferase Polymorphism in Iraqi Paediatric Patients with Acute Lymphoblastic Leukaemia

机译：伊拉克小儿急性淋巴细胞白血病患者硫嘌呤S-甲基转移酶多态性

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Acute Lymphoblastic Leukaemia (ALL) treatment protocols widely used thiopurine drugs as an anti-cancer agent, which over the course of time results in drug toxicity. Thiopurine S-Methyltransferase Enzyme (TPMT) is responsible for the activation of 6-Mercaptopurine (6-MP) to Thioguanine Nucleotides (TGNs) that are incorporated into DNA and trigger cell death. Low TPMT activity is strongly correlated to TPMT genetic polymorphism.Aim: To identify the level of TPMT activity and the most common TPMT polymorphism (TPMT*3A, TPMT*3B and TPMT*3C) and its frequencies in a sample of Iraqi ALL paediatric patients.Materials and Methods: Eighty-one Iraqi ALL paediatric patients receiving 6-MP in the maintenance phase of treatment were enrolled in the study. TPMT activity in the serum was measured by using Enzyme-Linked Immunosorbent Assay Technique (ELISA) in the serum and TPMT genetic polymorphism (TPMT*3A, TPMT*3B and TPMT*3C) was detected by allele-specific multiplex-PCR analysis. Statistical analysis was performed by using a two-sample t-test to evaluate the difference in allele frequencies proportion in TPMT polymorphism. Pearson?s correlation analysis was done to determine the correlation between TPMT enzyme genotype and phenotype.Results: There were 51 paediatric ALL patients carrying the wild-type allele with allele frequencies of (62.96%), 30 paediatric ALL patients carrying the mutant alleles either TPMT*3A or TPMT*3C with allele frequencies of 29.62% and 7.4% respectively. The mutant allele TPMT*3B was not detected in the patients under study. The difference in mean of the TPMT enzyme activity between the ALL patients carrying the wild-type allele and the mutant allele was highly significant with p-value =0.001. A highly significant positive co-relation (r=0.939) was found between TPMT low activity and presence of genetic mutation across the TPMT gene (p-value=0.001).Conclusion: TMPT genotyping and phenotyping is an essential tool to reduce the cytotoxic effects of the anti-cancer drug 6-MP in Iraqi paediatric patients with ALL for a successful recovery.
机译：急性淋巴细胞白血病（ALL）治疗方案广泛使用硫嘌呤类药物作为抗癌剂，随着时间的流逝会导致药物毒性。硫嘌呤S-甲基转移酶（TPMT）负责将6-巯基嘌呤（6-MP）激活为硫鸟嘌呤核苷酸（TGNs），并结合到DNA中并触发细胞死亡。较低的TPMT活性与TPMT遗传多态性密切相关。目标：在伊拉克人的样本中，确定TPMT活性水平和最常见的TPMT多态性（TPMT * 3A，TPMT * 3B和TPMT * 3C）及其频率所有儿科患者。材料与方法：本研究招募了八十一名在维持治疗阶段接受6-MP治疗的伊拉克所有儿科患者。通过使用酶联免疫吸附测定技术（ELISA）测定血清中TPMT活性，并通过等位基因特异性多重PCR分析检测TPMT遗传多态性（TPMT * 3A，TPMT * 3B和TPMT * 3C）。通过使用两个样本的t检验进行统计学分析，以评估TPMT多态性中等位基因频率比例的差异。结果进行了皮尔逊相关分析，确定了TPMT酶基因型与表型之间的相关性。结果：有51例携带野生型等位基因的小儿ALL患者，等位基因频率为（62.96％），有30例携带ALL等位基因的儿科ALL患者TPMT * 3A或TPMT * 3C等位基因频率分别为29.62％和7.4％的突变等位基因。在研究的患者中未检测到突变等位基因TPMT * 3B。携带野生型等位基因的所有患者和突变型等位基因的所有患者之间的TPMT酶活性均值差异非常显着，p值= 0.001。发现TPMT低活性与整个TPMT基因存在基因突变之间存在高度显着的正相关性（r = 0.939）（p值= 0.001）。结论：TMPT基因分型和表型分型是减少PTMT基因分型的重要工具。抗癌药6-MP对伊拉克小儿ALL患者的细胞毒性作用，可成功康复。

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