The effect of SNPs in CYP450 in chloroquine/primaquine Plasmodium vivax malaria treatment

Sortica, Vinicius A; Lindenau, Juliana D; Cunha, Maristela G; Ohnishi, Maria DO; Ventura, Ana Maria R; Ribeiro-dos-Santos, Ândrea KC; Santos, Sidney EB; Guimarães, Luciano SP; Hutz, Mara H

BACKGROUND: Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region. AIMS: This study investigates CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 genetic polymorphisms influence on cloroquine/primaquine treatment. PATIENTS & METHODS: Generalized estimating equations analyses were performed to determine the genetic influence in parasitemia and/or gametocytemia clearance over treatment time in 164 patients. RESULTS: An effect of CYP2C8 low-activity alleles on treatment was observed (p = 0.01). From baseline to first day of treatment, wild-type individuals achieved greater reduction of gametocytes than low-activity allele carriers. CYP2C9 and CYP3A5 genes showed a trend for gametocytemia and parasitemia clearance rates. CONCLUSION: Future studies should be performed to access the extent of CYP2C8, CYP2C9 and CYP3A5 gene polymorphisms influence on cloroquine/primaquine treatment.