Patterns of pharmacogenetic diversity in African populations: role of ancient and recent history

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Elisabete Oliveira (Author) Other; Rui Pereira (Author) Other; Antonio Amorim (Author) FCUP; Howard McLeod (Author) Other; Maria Joao Prata (Author) FCUP

Journal

Title: Pharmacogenomics

Vol. 10

Pages: 1413-1422

ISSN: 1462-2416

Publisher: ASHLEY PUBLICATIONS LTD

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 9 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-003-GFA

DOI: 10.2217/pgs.09.74

Abstract (EN): 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 Sao Tome e Principe (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 Sao Tome e Principe than in Cabinda or Mozambique. Admixture analysis demonstrated that the European contribution to the population of Sao Tome e Principe amounted to 13.3 +/- 3.3%. Furthermore, the proportion of African or European pharmacogenetic ancestry varied widely across each Sao Tomean individual. Discussion & conclusion: This implies that genetic association studies conducted in Sao Tome e Principe 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 Sao Tome e Principe 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10