CYP2C8 polymorphism frequencies among malaria patients in Zanzibar

Eur J Clin Pharmacol. 2005 Mar;61(1):15-8. doi: 10.1007/s00228-004-0871-8. Epub 2005 Jan 27.

Abstract

Objective: The determination of the prevalence of the CYP2C8 main alleles in a typical set of malaria patients in Zanzibar, as these patients represent a typical population exposed to amodiaquine, an antimalarial mainly metabolized by CYP2C8. Also, to determine for the first time the frequencies of CYP2C8 alleles in native African populations.

Methods: Polymerase chain reaction-restriction fragment polymorphism for the identification of CYP2C8*1, CYP2C8*2, CYP2C8*3 and CYP2C8*4 on a random population of 165 unrelated malaria patients.

Results: The allele frequencies found were: CYP2C8*1 (wild type, 83.4%), CYP2C8*2 (13.9%), CYP2C8*3 (2.1%) and CYP2C8*4 (0.6%). In terms of genotypes, 70.4% of the patients showed the CYP2C8*1/ CYP2C8*1 genotypes, while heterozygous between the wild type and other minor alleles were seen in 26.0%. Finally, 3.6% of the patients were homozygous for slow metabolizer alleles. The frequencies observed are equivalent to those documented for African-Americans.

Conclusions: CYP2C8 non-wild type alleles have a significant prevalence in the East African population studied. The consequent frequency of 3.6% of patients homozygous for slow metabolizer alleles represent a significant fraction of the population potentially in higher risk of adverse effects due to a less efficient metabolism of amodiaquine. As approximately 10(6) first-line treatments are currently performed in Zanzibar per year, this represents a non-negligible absolute number of amodiaquine exposures. This information constitutes a background for the pharmacovigilance programs presently being employed in Zanzibar.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amodiaquine / metabolism*
  • Amodiaquine / therapeutic use
  • Antimalarials / metabolism*
  • Antimalarials / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Child, Preschool
  • Cytochrome P-450 CYP2C8
  • Female
  • Humans
  • Infant
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / metabolism*
  • Male
  • Pharmacogenetics
  • Polymorphism, Genetic*
  • Prevalence
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tanzania

Substances

  • Antimalarials
  • Amodiaquine
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C8 protein, human
  • Cytochrome P-450 CYP2C8