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Race does not explain genetic heterogeneity in pharmacogenomic pathways

机译:种族不能解释药物基因组学途径中的遗传异质性

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Introduction: Polymorphic alleles in the human genome have been identified as affecting numerous drug responses. Currently, genotyping of all patients before starting a drug regimen is impractical. Since many polymorphisms occur at varying rates in different racial groups, we investigated whether a patient’s race could predict presence of drug-relevant genetic variants well enough to be used as a substitute for individual genotyping. Methods: We performed hierarchical clustering and principal components analysis on tagSNPs from three pathways (irinotecan, 5-fluorouracil and insulin) across 270 individuals from four racial groups available from the International HapMap Project. Results: For the drug pathways, irinotecan and 5-fluorouracil, individuals from each race were widely dispersed, although several subclusters consisted entirely of individuals from a single racial group. Principal components analysis confirmed race was not a major contributor to the SNP data variance. Interestingly, individuals tended to cluster more by race across the endogenous insulin signaling pathway SNPs. Conclusions: Most genetic variation was determined by individual variation, not racial grouping, indicating race is not adequate as a surrogate to individualized therapy.
机译:简介:已经确定了人类基因组中的多态性等位基因会影响许多药物反应。目前,在开始药物治疗之前对所有患者进行基因分型是不切实际的。由于在不同种族中许多多态性以不同的速度发生,因此我们调查了患者的种族是否可以很好地预测与药物相关的遗传变异的存在,从而可以替代个体基因分型。方法:我们对来自国际HapMap项目的四个种族的270个人的三个途径(伊立替康,5-氟尿嘧啶和胰岛素)的tagSNPs进行了分级聚类和主成分分析。结果:对于药物途径,伊立替康和5-氟尿嘧啶,每个种族的个体分布广泛,尽管几个亚族完全由一个种族组成。主成分分析证实种族不是SNP数据差异的主要因素。有趣的是,个体倾向于通过内源性胰岛素信号传导途径SNPs的种族聚类。结论:大多数遗传变异是由个体变异而不是种族分组决定的,这表明种族不足以替代个体化治疗。

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