Distribution of the cytochrome P450 CYP2C8*2 allele in Brazzaville, Republic of Congo.

BACKGROUND

Cytochrome P450 (CYP) enzymes are essential in the metabolism of most drugs used today. Single nucleotide polymorphism(s) occurring in CYP genes can adversely affect drug pharmacokinetics, efficacy, and safety. Individuals carrying the CYP2C82 c.805A > T (CYP2C82; rs11572103) allele have impaired amodiaquine metabolism, increased risk of amodiaquine-related adverse events, and may promote the selection of drug-resistant parasite strains. This study investigated the distribution of the CYP2C8*2 allele in Brazzaville, Republic of Congo, where artesunate + amodiaquine is used as the second-line treatment for uncomplicated Plasmodium falciparum malaria.

METHODS

A total of 285 febrile children visiting the Marien Ngouabi paediatric hospital were genotyped for CYP2C8*2 using PCR-restriction fragment length polymorphism (PCR-RFLP). The allele frequencies and genotype distribution were determined.

RESULTS

The CYP2C82 allele was successfully genotyped in 75% (213/285) of the study participants. The CYP2C82A allele had a frequency of 63%, whereas the CYP2C82T allele had a frequency of 37%. Genotypes CYP2C82AA (rapid metabolizer), CYP2C82AT (intermediate metabolizer), and CYP2C82TT (poor metabolizer) were observed in 44%, 38%, and 18% of the investigated participants, respectively.

CONCLUSIONS

This study gives the first description of CYP2C8*2 allele distribution in the Republic of Congo and highlights the potential risk of amodiaquine-related adverse events. Information from this study will be beneficial during pharmacovigilance investigations.