title: Influence of genomic ancestry on the distribution of SLCO1B1, SLCO1B3 and ABCB1 gene polymorphisms among Brazilians.
abstract: The frequency distribution of SNPs and haplotypes in the ABCB1, SLCO1B1 and SLCO1B3 genes varies largely among continental populations. This variation can lead to biases in pharmacogenetic studies conducted in admixed populations such as those from Brazil and other Latin American countries. The aim of this study was to evaluate the influence of self-reported colour, geographical origin and genomic ancestry on distributions of the ABCB1, SLCO1B1 and SLCO1B3 polymorphisms and derived haplotypes in admixed Brazilian populations. A total of 1039 healthy adults from the north, north-east, south-east and south of Brazil were recruited for this investigation. The c.388A>G (rs2306283), c.463C>A (rs11045819) and c.521T>C (rs4149056) SNPs in the SLCO1B1 gene and c.334T>G (rs4149117) and c.699G>A (rs7311358) SNPs in the SLCO1B3 gene were determined by Taqman 5'-nuclease assays. The ABCB1 c.1236C>T (rs1128503), c.2677G>T/A (rs2032582) and c.3435C>T (rs1045642) polymorphisms were genotyped using a previously described single-base extension/termination method. The results showed that genotype and haplotype distributions are highly variable among populations of the same self-reported colour and geographical region. However, genomic ancestry showed that these associations are better explained by a continuous variable. The influence of ancestry on the distribution of alleles and haplotype frequencies was more evident in variants with large differences in allele frequencies between European and African populations. Design and interpretation of pharmacogenetic studies using these transporter genes should include genomic controls to avoid spurious conclusions based on improper matching of study cohorts from Brazilian populations and other highly admixed populations.
authors.affiliation: Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Vinicius de A
authors.initials: Vde A
authors.lastname: Sortica
authors.forename: Elida B
authors.initials: EB
authors.lastname: Ojopi
authors.forename: Júlia P
authors.initials: JP
authors.lastname: Genro
authors.forename: Sidia
authors.initials: S
authors.lastname: Callegari-Jacques
authors.forename: Andrea
authors.initials: A
authors.lastname: Ribeiro-Dos-Santos
authors.forename: Manoel Odorico
authors.initials: MO
authors.lastname: de Moraes
authors.forename: Marco A
authors.initials: MA
authors.lastname: Romano-Silva
authors.forename: Sérgio D J
authors.initials: SD
authors.lastname: Pena
authors.forename: Guilherme
authors.initials: G
authors.lastname: Suarez-Kurtz
authors.forename: Mara H
authors.initials: MH
authors.lastname: Hutz
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D001938:Brazil; D015331:Cohort Studies; D005787:Gene Frequency; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D027381:Liver-Specific Organic Anion Transporter 1; D058990:Molecular Targeted Therapy; D027361:Organic Anion Transporters / Q000235:genetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics*; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3