Distribution of ABCB1 polymorphisms among Brazilians: impact of population admixture
| Autor: | Emmanuel Dias-Neto, Rita de Cássia Elias Estrela, Guilherme Suarez-Kurtz, Renato S. Carvalho, Fabio S. Ribeiro, Sheila P. Gregório, Claudio J. Struchiner |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male Linkage disequilibrium ATP Binding Cassette Transporter Subfamily B Genotype Population Molecular Sequence Data Single-nucleotide polymorphism Ancestry-informative marker Biology Population stratification Logistic regression Polymorphism Single Nucleotide Linkage Disequilibrium Polymorphism (computer science) Genetics Humans ATP Binding Cassette Transporter Subfamily B Member 1 education DNA Primers Pharmacology education.field_of_study Polymorphism Genetic Base Sequence Racial Groups Exons Single-base extension Genetics Population Molecular Medicine Regression Analysis Female Brazil |
| Zdroj: | Pharmacogenomics. 9(3) |
| ISSN: | 1744-8042 |
| Popis: | Introduction: 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 ( 0.75 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. Conclusion: 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. |
| Databáze: | OpenAIRE |
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