Distribution of ABCB1 polymorphisms among Brazilians: impact of population admixture
Distribution of ABCB1 polymorphisms among Brazilians: impact of population admixture
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DOI：
10.2217/14622416.9.3.267
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发表时间：
2008-03-01
期刊：
影响因子：
2.1
通讯作者：
Suarez-Kurtz, Guilherme
中科院分区：
文献类型：
--
作者：
Estrela, Rita C. E.;Ribeiro, Fabio S.;Suarez-Kurtz, Guilherme
简介：种族间混合是神秘群体结构的一个来源，可能导致药物基因组学研究中虚假的基因型-表型关联。我们研究了巴西人中人口分层对 ABCB1 多态性（1236C > T、2677G > T/A 和 3435C > T）分布的影响，巴西人是一个具有美洲印第安人、欧洲人和非洲祖先的高度混合的人群。方法：使用一组血统信息标记对 320 名健康成年人的个体 DNA 进行基因分型，并估计非洲血统成分 (ACA) 的比例。 ABCB1 基因型通过单碱基延伸/终止方法确定。我们通过对数据拟合线性比例优势逻辑回归模型来描述 ABCB1 多态性和 ACA 之间的关联。结果：ABCB1 2677G > T/A 和 3435C > T，但不是 1236C > T，SNP 的分布显示出从白人到中级到黑人个体 T 等位基因和 TT 基因型频率下降的显着趋势。在 1236、2677 和 3435 个基因座的 T/nonG/T 单倍型频率中观察到相同的趋势。当人口样本按四分位数比例时，根据个体 ACA 估计，每个位点的 T 等位基因和 TT 基因型的频率从最低 (< 0.25 ACA) 到最高 (> 0.75 ACA) 四分位数逐渐下降。线性比例优势逻辑回归分析证实，在整个群体样本中观察到的整个 ACA 范围 (0.13-0.94) 中，每个基因座具有 T 等位基因的几率随着 ACA 的增加而连续下降。在个体 ACA 估计值与总体人群中 T/nonG/T 单倍型的存在之间也发现了显着的关联。结论：根据巴西人口普查提出的种族/肤色类别进行自我识别不足以正确控制 ABCB1 药物基因组学研究中的人群分层。
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 (< 0.25 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. 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.