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

• Published in: Pharmacogenomics Vol. 24; no. 11; pp. 583 - 597
• Main Authors: Cramer, Estee Y, Bartlett, Jacquelaine, Chan, Ernest R, Gaedigk, Andrea, Ratsimbasoa, Arsene C, Mehlotra, Rajeev K, Williams, Scott M, Zimmerman, Peter A
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.07.2023
• Subjects: Antimalarials - therapeutic use; Chloroquine - therapeutic use; copy number variation; DNA Copy Number Variations - genetics; genome-wide array; Genome-Wide Association Study; Humans; Madagascar; malaria treatment; Pharmacogenetics; primaquine; Primaquine - therapeutic use; Plasmodium vivax; Madagascar; genome-wide array; primaquine; copy number variation; malaria treatment
• ISSN: 1462-2416; 1744-8042; 1744-8042
• DOI: 10.2217/pgs-2023-0091

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.