Patterns of Pharmacogenetic Diversity in African Populations: Role of Ancient and Recent History

Abstract

Aims: The knowledge that genetic variation influencing drug response is clearly structured among human populations has prompted many studies aimed at obtaining pharmacogenetic profiles in specific populations. While large amounts of data are being produced for populations from developed countries, the African continent still remains very poorly studied. To help to fill this gap, this work characterized three previously uncharacterized African populations for a set of pharmacogenetically relevant polymorphisms. Materials & methods: Seven polymorphic variations in four genes that encode enzymes from phase I (CYP2C9, CYP3A4 and CYP3A5) or phase III (ABCB1) of drug metabolism were analyzed in population samples from Cabinda (n = 107), Mozambique (n = 109) and São Tomé e Príncipe (n = 126). All three populations shared strong recent historical links with Portugal. Results: The majority of the screened variations displayed large contrasts in allele frequencies between European and African populations, and this study identified a substantial higher European influence in São Tomé e Príncipe than in Cabinda or Mozambique. Admixture analysis demonstrated that the European contribution to the population of São Tomé e Príncipe amounted to 13.3 ± 3.3%. Furthermore, the proportion of African or European pharmacogenetic ancestry varied widely across each São Tomean individual. Discussion & conclusion: This implies that genetic association studies conducted in São Tomé e Príncipe should take into account the confounding factor of admixture to avoid spurious positive or negative results. Our findings also indicate that drug dosage requirements may be different in São Tomé e Príncipe than in other African populations. Thus, the search for pharmacogenetic risk factors should be assessed at an individual level, therefore fulfilling the perspective of personalized medicine. This study further indicates that the common notion of ‘African population‘ might hide a pattern of pharmacogenetic heterogeneity whose real extent still needs to be evaluated by means of a refined sampling of the entire continent.

KEYWORDS::

• admixture
• African populations
• population-based pharmacogenetics

Financial & competing interests disclosure

This work was partially supported by the national Fundação para a Ciência e Tecnologia (FCT) through grant SFRH/BD/17124/2004 and the NIH Pharmacogenetics Research Network (U01 GM63340). IPATIMUP is partially supported by ‘Programa Operacional Ciência e Inovação 2010‘ (POCI 2010). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was partially supported by the national Fundação para a Ciência e Tecnologia (FCT) through grant SFRH/BD/17124/2004 and the NIH Pharmacogenetics Research Network (U01 GM63340). IPATIMUP is partially supported by ‘Programa Operacional Ciência e Inovação 2010‘ (POCI 2010). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.