title: Distribution of ABCB1 polymorphisms among Brazilians: impact of population admixture.
abstract: BACKGROUND
  Interethnic admixture is a source of cryptic population structure that may lead to spurious genotype-phenotype associations in pharmacogenomic studies. We studied the impact of population stratification on the distribution of ABCB1 polymorphisms (1236C>T, 2677G>T/A and 3435C>T) among Brazilians, a highly admixed population with Amerindian, European and African ancestral roots.
  
  
  METHODS
  Individual DNA from 320 healthy adults was genotyped with a panel of ancestry informative markers, and the proportions of African component of ancestry (ACA) were estimated. ABCB1 genotypes were determined by the single base extension/termination method. We describe the association between ABCB1 polymorphisms and ACA by fitting a linear proportional odds logistic regression model to the data.
  
  
  RESULTS
  The distribution of the ABCB1 2677G>T/A and 3435C>T, but not the 1236C>T, SNPs displayed a significant trend for decreasing frequency of the T alleles and TT genotypes from White to Intermediate to Black individuals. The same trend was observed in the frequency of the T/nonG/T haplotype at the 1236, 2677 and 3435 loci. When the population sample was proportioned in quartiles, according to the individual ACA estimates, the frequency of the T allele and TT genotype at each locus declined progressively from the lowest (< 0.25 ACA) to the highest (> 0.75 ACA) quartile. Linear proportional odds logistic regression analysis confirmed that the odds of having the T allele at each locus decreases in a continuous manner with the increase of the ACA, throughout the ACA range (0.13-0.94) observed in the overall population sample. A significant association was also detected between the individual ACA estimates and the presence of the T/nonG/T haplotype in the overall population.
  
  
  CONCLUSIONS
  Self-identification according to the racial/color categories proposed by the Brazilian Census is insufficient to properly control for population stratification in pharmacogenomic studies of ABCB1.
authors.affiliation: Divisão de Farmacologia, Instituto Nacional de Câncer, Rua André Cavalcanti 37, Rio de Janeiro 21230-050, Brazil.
authors.forename: Rita C E
authors.initials: RC
authors.lastname: Estrela
authors.forename: Fábio S
authors.initials: FS
authors.lastname: Ribeiro
authors.forename: Renato S
authors.initials: RS
authors.lastname: Carvalho
authors.forename: Sheila P
authors.initials: SP
authors.lastname: Gregório
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dias-Neto
authors.forename: Cláudio J
authors.initials: CJ
authors.lastname: Struchiner
authors.forename: Guilherme
authors.initials: G
authors.lastname: Suarez-Kurtz
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D001938:Brazil; D017931:DNA Primers; D005091:Exons; D005260:Female; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics; D012044:Regression Analysis
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers