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马达加斯加人群的药物基因组学变异:对抗疟药物伯氨喹代谢的影响。

Pharmacogenomic variation in the Malagasy population: implications for the antimalarial drug primaquine metabolism.

机构信息

Center for Global Health & Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.

Department of Biostatistics & Epidemiology, School of Public Health & Health Sciences, University of Massachusetts Amherst, Amherst, MA 01003, USA.

出版信息

Pharmacogenomics. 2023 Jul;24(11):583-597. doi: 10.2217/pgs-2023-0091. Epub 2023 Aug 8.

Abstract

Antimalarial primaquine (PQ) eliminates liver hypnozoites of   gene variation contributes to PQ therapeutic failure. Additional gene variation may contribute to PQ efficacy. Information on pharmacogenomic variation in Madagascar, with malaria and a unique population admixture, is scanty. The authors performed genome-wide genotyping of 55 Malagasy samples and analyzed data with a focus on a set of 28 pharmacogenes most relevant to PQ. Mainly, the study identified 110 coding or splicing variants, including those that, based on previous studies in other populations, may be implicated in PQ response and copy number variation, specifically in chromosomal regions that contain pharmacogenes. With this pilot information, larger genome-wide association analyses with PQ metabolism and response are substantially more feasible.

摘要

抗疟药伯氨喹(PQ)消除肝休眠疟原虫的能力。基因变异有助于 PQ 治疗失败。其他基因变异可能有助于 PQ 的疗效。马达加斯加疟疾流行,人群混合独特,但有关其药物基因组学变异的信息很少。作者对 55 个马达加斯加样本进行了全基因组基因分型,并对一组 28 个与 PQ 最相关的药物基因进行了数据分析。该研究主要发现了 110 个编码或剪接变异,包括根据其他人群的先前研究,可能与 PQ 反应和拷贝数变异有关的变异,特别是在含有药物基因的染色体区域。有了这个初步信息,进行更大规模的与 PQ 代谢和反应相关的全基因组关联分析就更加可行了。

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