Genetics Department, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Basic Clin Pharmacol Toxicol. 2012 May;110(5):460-8. doi: 10.1111/j.1742-7843.2011.00838.x. Epub 2011 Dec 29.
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.
SNP 和单倍型在 ABCB1、SLCO1B1 和 SLCO1B3 基因中的频率分布在大陆人群中差异很大。这种变异可能导致在巴西和其他拉丁美洲国家等混合人群中进行的遗传药理学研究出现偏差。本研究旨在评估自我报告的肤色、地理起源和基因组祖先对混合巴西人群中 ABCB1、SLCO1B1 和 SLCO1B3 多态性和衍生单倍型分布的影响。共招募了来自巴西北部、东北部、东南部和南部的 1039 名健康成年人参与本研究。采用 Taqman 5'-核酸酶检测法检测 SLCO1B1 基因的 c.388A>G(rs2306283)、c.463C>A(rs11045819)和 c.521T>C(rs4149056)SNP，以及 SLCO1B3 基因的 c.334T>G(rs4149117)和 c.699G>A(rs7311358)SNP。采用先前描述的单碱基延伸/终止法检测 ABCB1 c.1236C>T(rs1128503)、c.2677G>T/A(rs2032582)和 c.3435C>T(rs1045642)多态性。结果表明，同一自我报告肤色和地理区域的人群中，基因型和单倍型分布高度可变。然而，基因组祖先表明，这些关联可以通过连续变量更好地解释。在欧洲和非洲人群中等位基因频率差异较大的变异体中，遗传背景对等位基因和单倍型频率分布的影响更为明显。使用这些转运蛋白基因进行遗传药理学研究的设计和解释应包括基因组对照，以避免基于巴西人群和其他高度混合人群研究队列的不当匹配得出虚假结论。
