Application of the F sub(ST) statistics to explore pharmacogenomic diversity in the Brazilian population

• Published in: Pharmacogenomics Vol. 13; no. 7; pp. 771 - 777
• Main Authors: Suarez-Kurtz, Guilherme, Pena, Sergio DJ, Hutz, Mara H
• Format: Journal Article
• Language: English
• Published: 01.05.2012
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs.12.39

Background: New drug applications submitted to regulatory agencies in developing countries rarely include data from local clinical trials. We used the F sub(ST) statistics to explore the pharmacogenomic diversity of the Brazilian population and its potential implications in drug regulatory assessment and decisions. Methods: The F sub(ST) analyses were based on data for 44 polymorphisms in 12 pharmacogenes among 1034 healthy Brazilians, recruited in four different geographical regions and self-identified as branco (white) pardo (brown) or preto (black). Each region/color group comprised 83-89 individuals. The Utah residents of northern and western European ancestry and Yoruba people from Nigeria, Africa, cohorts of the HapMap project were used as proxies of the European and sub-Saharan African ancestral roots of Brazilians, respectively. Results: Allele-specific F sub(ST) values for the overall Brazilian cohort revealed low genetic divergence between white and brown (F sub(ST) = 0.005 plus or minus 0.006, mean plus or minus standard deviation), white and black (0.013 plus or minus 0.017) and brown and black (0.004 plus or minus 0.005) individuals. However, the distribution of F sub(ST) values for white vs brown (p < 0.0001, analysis of variance) and white vs black (p < 0.0001) differed significantly across the geographical regions. Considerably larger pharmacogenomic divergence was observed between black Brazilians and Yoruba people from Nigeria, Africa (F sub(ST) = 0.028 plus or minus 0.035) compared to white Brazilians vs Utah residents of northern and western European ancestry (0.007 plus or minus 0.010). Conclusion: The present F sub(ST) analyses highlight the challenge faced by Brazilian regulatory agencies when assessing the relevance to Brazilians of pharmacogenomic data derived from foreign populations, with distinct biogeographical ancestries. This challenge is compounded by the heterogeneity of the Brazilian population with respect to the frequency distribution of pharmacogenomic polymorphisms across color categories and geographical regions. Original submitted 19 December 2011; Revision submitted 27 February 2012