Malaria pharmacogenetics in Botswana: interethnic differences and public health.

Human cytochrome P450 2C8 and 2B6 are two highly polymorphic genes and show variation according to ethnicity. They are very important drug-metabolism genes in tropical medicine since the respective liver enzymes are involved in the metabolism of antimalarial drugs chloroquine, amodiaquine (CYP2C8) and artemisinin derivatives (CYP2B6). The CYP2C8*2, CYP2B6*6, CYP2B6*16, CYP2B6*18 alleles are slow drug metabolism alleles and show high frequency in Black populations. The objective of this study was to assess their prevalence in Botswana among the San (or Bushmen) and the Bantu ethnic groups. For that purpose we recruited 544 children of the two ethnicities in three districts of Botswana from primary schools, collected blood samples, extracted DNA and genotyped them through PCR-based restriction fragment length polymorphism analysis. The results demonstrated that in the San the prevalence of the CYP2C8*2 allele is significantly higher than among the Bantu-related ethnic groups, as well as is lower the prevalence of the CYP2B6 alleles. These findings support the evidence of a different genetic background of the San with respect to Bantu-related populations, and highlight a possible higher risk of variable drug clearance and/or activation of pro-drugs CYP2C8 and CYP2B6-mediated among the San group to respect the Bantu of Botswana.