Prevalence in Northern Angola of Cytochrome P450 (CYP) 2C8 Alleles Associated with Amodiaquine Decreased Metabolism

安哥拉北部与阿莫地喹代谢降低相关的细胞色素P450(CYP)2C8等位基因的流行情况

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Abstract

Amodiaquine-artesunate is one of the recommended options by the Angolan National Malaria Control Program for the treatment of uncomplicated malaria and for malaria seasonal chemoprevention. CYP2C8 is a critical enzyme in the metabolism of amodiaquine. The CYP2C8 gene harbors alleles coding for less active enzymes that have been linked to amodiaquine-associated adverse events. In this work, we analyzed the prevalences of the CYP2C8 main alleles in a sample of the Angolan population. We found an expected robust frequency of a very-low-activity allele, CYP2C8*2 (18.2%) but also the unusual presence of alleles CYP2C8*3 (1%) and CYP2C8*4 (0.5%). Together, these alleles were seen in a non-negligible group of Plasmodium falciparum malaria patients and children under amodiaquine-based therapies and prophylactic strategies.

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