Pharmacogenomic Diversity among Brazilians: Influence of Ancestry, Self-Reported Color, and Geographical Origin

Abstract

By virtue of being the product of the genetic admixture of three ancestral roots: Europeans, Africans, and Amerindians, the present-day Brazilian population displays very high levels of genomic diversity, which have important pharmacogenetic/-genomic (PGx) implications. Recognition of this fact has prompted the creation of the Brazilian Pharmacogenomics Network (Refargen), a nationwide consortium of research groups, with the mission to provide leadership in PGx research and education in Brazil, with a population heath impact. Here, we present original data and review published results from a Refargen comprehensive study of the distribution of PGx polymorphisms in a representative cohort of the Brazilian people, comprising 1,034 healthy, unrelated adults, self-identified as white, brown, or black, according to the Color categories adopted by the Brazilian Census. Multinomial log-linear regression analysis was applied to infer the statistical association between allele, genotype, and haplotype distributions among Brazilians (response variables) and self-reported Color, geographical region, and biogeographical ancestry (explanatory variables), whereas Wright’s FST statistics was used to assess the extent of PGx divergence among different strata of the Brazilian population. Major PGx implications of these findings are: first, extrapolation of data from relatively well-defined ethnic groups is clearly not applicable to the majority of Brazilians; second, the frequency distribution of polymorphisms in several pharmacogenes of clinical relevance (e.g., ABCB1, CYP3A5, CYP2C9, VKORC) varies continuously among Brazilians and is not captured by race/Color self-identification; third, the intrinsic heterogeneity of the Brazilian population must be acknowledged in the design and interpretation of PGx studies in order to avoid spurious conclusions based on improper matching of study cohorts.

CCR5Δ32 (rs333) polymorphism is associated with the susceptibility to systemic lupus erythematosus in female Brazilian patients

“…The most of Brazilians are European-descending [33], and the overall frequency of CCR5Δ32 variant allele was 0.0418 and varied in different ethnic groups, such as 0.0504 among Caucasians, 0.0280 among Browns, and absent in Blacks and Asians [34].…”

Pharmacogenomic Implications of Population Admixture: Brazil as a Model Case

“…Brazil has been the main source of pharmacogenetics information in Latin American countries [3] and hosts a pharmacogenomics network, the Rede Nacional de Farmacogenômica (Refargen [4,104]), which presently congregates 18 research groups from four different geographical regions of the country. Refargen's mission is to provide leadership in pharmacogenomics research and education, with a population health impact.…”

Pvuii Genetic Polymorphism of Low Density Lipoprotein Receptorin Human Immunodeficiency Virus Type 1-Infected Patients: Possible Association with Dyslipidemia

“…Brazilian is one of the most genetically heterogeneous population worldwide, as the result of five centuries of interethnic crosses between peoples from three continents (Amerindians, Europeans and Africans) [21], the distribution pattern of the PvuII LDLR intron 15 genotypes obtained in the present cohort of HIV-1-infected patients seems to be similar to those observed in hypercholesterolemic patients from Israel, Italy, Spain, Netherlands and Denmark, London, North America, Switzerland, and Germany [18,[22][23][24]. The frequency of the P1P1, P1P2 and P2P2 genotypes obtained among the Italian population was 46.4%, 43.2%, and 10.4%, respectively, and the P1 and P2 allelic frequency was 0.680 and 0.320, respectively [25].…”