Exploring the distribution of genetic markers of pharmacogenomics relevance in Brazilian and Mexican populations

PLoS One. 2014 Nov 24;9(11):e112640. doi: 10.1371/journal.pone.0112640. eCollection 2014.

Abstract

Studies of pharmacogenomics-related traits are increasingly being performed to identify loci that affect either drug response or susceptibility to adverse drug reactions. However, the effect of the polymorphisms can differ in magnitude or be absent depending on the population being assessed. We used the Affymetrix Drug Metabolizing Enzymes and Transporters (DMET) Plus array to characterize the distribution of polymorphisms of pharmacogenetics and pharmacogenomics (PGx) relevance in two samples from the most populous Latin American countries, Brazil and Mexico. The sample from Brazil included 268 individuals from the southeastern state of Rio de Janeiro, and was stratified into census categories. The sample from Mexico comprised 45 Native American Zapotecas and 224 self-identified Mestizo individuals from 5 states located in geographically distant regions in Mexico. We evaluated the admixture proportions in the Brazilian and Mexican samples using a panel of Ancestry Informative Markers extracted from the DMET array, which was validated with genome-wide data. A substantial variation in ancestral proportions across census categories in Brazil, and geographic regions in Mexico was identified. We evaluated the extent of genetic differentiation (measured as FST values) of the genetic markers of the DMET Plus array between the relevant parental populations. Although the average levels of genetic differentiation are low, there is a long tail of markers showing large frequency differences, including markers located in genes belonging to the Cytochrome P450, Solute Carrier (SLC) and UDP-glucuronyltransferase (UGT) families as well as other genes of PGx relevance such as ABCC8, ADH1A, CHST3, PON1, PPARD, PPARG, and VKORC1. We show how differences in admixture history may have an important impact in the distribution of allele and genotype frequencies at the population level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brazil
  • Cytochrome P-450 CYP2D6 / genetics
  • Gene Frequency
  • Genetic Loci / genetics*
  • Genetics, Population / methods
  • Genotype
  • Glucuronosyltransferase / genetics
  • Haplotypes*
  • Humans
  • Logistic Models
  • Mexico
  • Pharmacogenetics / methods*
  • Polymorphism, Single Nucleotide*
  • Vitamin K Epoxide Reductases / genetics

Substances

  • Cytochrome P-450 CYP2D6
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases
  • UGT1A1 enzyme
  • Glucuronosyltransferase

Grants and funding

FUNDERS: (1) Funding supported by Conselho Nacional do Desenvolvimento Científico (CNPq) CNPq no. 304063/2011-8, http://www.cnpq.br (GS-K). (2) Funding supported by Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) FAPERJ no. E-26/102796/2012, URL: http://www.faperj.br; FAPERJ no. E-26/110683/2012, URL: http://www.faperj.br (GS-K). (3) Funding supported by Financiadora de Estudos e Projetos (FINEP) FINEP no. 01.08.0123.00, URL: http://www.finep.gov.br (GS-K). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. SPONSORSHIPS: (1) The Affymetrix DMETplus chips were provided by the Pharmacogenetics for every nation initiative (PGENI), a USA-based global health non-profit organization. PGENI is supported by individual donors and does not solicit funding from health care-oriented companies. (2) The Affymetrix DMET Plus array data for the European, African and East Asian HapMap samples were provided by Affymetrix Inc.