Pharmacogenetics of 6-mercaptopurine in a black Zimbabwean cohort treated for acute lymphoblastic leukaemia.

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY Pharmacogenomics Pub Date : 2023-06-01 Epub Date: 2023-05-30 DOI:10.2217/pgs-2023-0026

Pageneck Chikondowa, Derick Munkombwe, Zedias Chikwambi, Patience Kuona, Collen Masimirembwa

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Abstract

Background: 6-mercaptopurine usage is associated with myelotoxicity and increased risk in patients carrying metabolism-related genetic variations. This study aimed to determine the frequency of candidate gene polymorphisms and their association with 6-mercaptopurine intolerance. Methods: A total of 41 patients on acute lymphoblastic leukaemia treatment were genotyped for TPMT and NUDT15 (rs116855232) alleles, and their association with dose intensity was analyzed. Results: The defective TPMT*3C allele frequency was 9.8%. The median maintenance dose intensity for TPMT*1/*3C participants was considerably lower (47%) when compared with the TPMT*1/*1 wild-type (77%), although not statistically significant. Conclusion: This is the first pharmacogenetics study carried out in a black Zimbabwean leukemia patient cohort. The high defective TPMT*3C (9.8%) allele frequency points to the potential utility of pharmacogenetics testing for safe usage of 6-mercaptopurine in this population.

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津巴布韦黑人急性淋巴细胞白血病患者 6-巯基嘌呤的药物遗传学。

背景：6-巯基嘌呤的使用与骨髓毒性有关，并增加了携带代谢相关基因变异患者的风险。本研究旨在确定候选基因多态性的频率及其与 6-巯基嘌呤不耐受的关系。研究方法对41名接受急性淋巴细胞白血病治疗的患者进行了TPMT和NUDT15（rs116855232）等位基因的基因分型，并分析了它们与剂量强度的关系。结果发现有缺陷的 TPMT*3C 等位基因频率为 9.8%。与 TPMT*1/*1 野生型（77%）相比，TPMT*1/*3C 参与者的中位维持剂量强度要低得多（47%），但没有统计学意义。结论这是首次在津巴布韦黑人白血病患者群体中开展药物遗传学研究。高缺陷 TPMT*3C 等位基因频率（9.8%）表明，药物遗传学检测可能有助于该人群安全使用 6-巯基嘌呤。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.