Pharmacogenetics of praziquantel in Zimbabweans

The control of schistosomiasis, a parasitic disease contracted via contact with contaminated fresh water sources, is heavily reliant on the drug praziquantel (PZQ). For a treatment with PZQ to be successful, the patient must have a high enough concentration of the drug in circulation to kill the parasites. However, differences in the genetics of certain individuals can alter this response to PZQ and the success of a treatment, a mechanism termed pharmacogenetics. Despite the widespread use of PZQ in Africa, the characterisation of pharmacogenetics in African populations has been scarce, with only one previous study published. Therefore, we aimed to identify pharmacogenetic differences associated with the success or failure of a treatment with PZQ using schistosome-infected Zimbabweans. Six enzymes key in PZQ metabolism were mapped to the Zimbabwean genomic DNA, to find variants significantly associated with the success or failure of a PZQ treatment. Overall, this study adds to the genomic characterisation of a diverse population in Africa and identified variants relevant to other pharmacogenetic studies crucial for the development and usage of drugs in these populations.

血吸虫病（schistosomiasis）是一种经接触受污染淡水感染的寄生虫病，其防控高度依赖吡喹酮（praziquantel，PZQ）。若要使吡喹酮治疗获得成功，患者循环系统中的药物浓度需达到足以杀灭寄生虫的水平。然而，部分个体的遗传差异会改变其对吡喹酮的反应及治疗结局，这一机制被称为药物遗传学（pharmacogenetics）。尽管吡喹酮在非洲应用广泛，但针对非洲人群的药物遗传学特征研究仍极为匮乏，迄今仅发表过一项相关研究。因此，本研究以感染血吸虫的津巴布韦人群为研究对象，旨在探寻与吡喹酮治疗成败相关的药物遗传学差异。研究人员针对与吡喹酮代谢密切相关的六种酶，对津巴布韦受试者的基因组DNA进行了基因定位分析，以筛选出与吡喹酮治疗成败显著相关的基因变异。总体而言，本研究丰富了非洲多元人群的基因组特征研究，并筛选出与其他药物遗传学研究相关的基因变异，此类变异对非洲人群的药物研发与临床应用均具有关键价值。