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Race does not explain genetic heterogeneity in pharmacogenomic pathways.


ABSTRACT: 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.

SUBMITTER: Yen-Revollo JL 

PROVIDER: S-EPMC2632586 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Race does not explain genetic heterogeneity in pharmacogenomic pathways.

Yen-Revollo Jane L JL   Auman J Todd JT   McLeod Howard L HL  

Pharmacogenomics 20081101 11


<h4>Introduction</h4>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.<h4>Methods</h4>We performed hierarchical clustering and  ...[more]

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