Race does not explain genetic heterogeneity in pharmacogenomic pathways.
BACKGROUND
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.
Yen-Revollo
Jane L
JL
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.
Auman
J Todd
JT
McLeod
Howard L
HL
D002166:Camptothecin / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D016000:Cluster Analysis; D030541:Databases, Genetic; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000494:pharmacology; D018740:Genetic Heterogeneity; D006801:Humans; D007328:Insulin / Q000493:pharmacokinetics / Q000494:pharmacology; D000077146:Irinotecan; D008657:Metabolic Clearance Rate; D010597:Pharmacogenetics / Q000379:methods* / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D044469:Racial Groups / Q000235:genetics*
D007328:Insulin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin