Yen-Revollo Jane L, Auman J Todd, McLeod Howard L
UNC Institute for Pharmacogenomics and Individualized Therapy, University of North Carolina, Chapel Hill, Campus Box 7360, 3203 Kerr Hall, Chapel Hill, NC 27599-7360, USA.
Pharmacogenomics. 2008 Nov;9(11):1639-45. doi: 10.2217/14622416.9.11.1639.
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.
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.
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.
Most genetic variation was determined by individual variation, not racial grouping, indicating race is not adequate as a surrogate to individualized therapy.
人类基因组中的多态性等位基因已被确定会影响多种药物反应。目前，在开始药物治疗方案前对所有患者进行基因分型是不切实际的。由于许多多态性在不同种族群体中的发生率各不相同，我们研究了患者的种族是否能够充分预测与药物相关的基因变异的存在，从而足以替代个体基因分型。
我们对来自国际人类基因组单体型图计划的四个种族群体的270名个体的三个通路（伊立替康、5-氟尿嘧啶和胰岛素）中的标签单核苷酸多态性（tagSNP）进行了层次聚类和主成分分析。
对于伊立替康和5-氟尿嘧啶这两种药物通路，每个种族的个体分布广泛，尽管有几个亚群完全由来自单一种族群体的个体组成。主成分分析证实种族不是SNP数据变异的主要因素。有趣的是，在内源性胰岛素信号通路的SNP中，个体往往按种族聚类得更多。
大多数基因变异是由个体差异决定的，而非种族分组，这表明种族不足以作为个体化治疗的替代指标。
