Race does not explain genetic heterogeneity in pharmacogenomic pathways

Pharmacogenomics. 2008 Nov;9(11):1639-45. doi: 10.2217/14622416.9.11.1639.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Camptothecin / analogs & derivatives
  • Camptothecin / pharmacokinetics
  • Camptothecin / pharmacology
  • Cluster Analysis
  • Databases, Genetic
  • Fluorouracil / pharmacokinetics
  • Fluorouracil / pharmacology
  • Genetic Heterogeneity*
  • Humans
  • Insulin / pharmacokinetics
  • Insulin / pharmacology
  • Irinotecan
  • Metabolic Clearance Rate
  • Pharmacogenetics / methods*
  • Pharmacogenetics / statistics & numerical data
  • Polymorphism, Single Nucleotide
  • Principal Component Analysis
  • Racial Groups / genetics*

Substances

  • Insulin
  • Irinotecan
  • Fluorouracil
  • Camptothecin