Race does not explain genetic heterogeneity in pharmacogenomic pathways.

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.

journal_name

Pharmacogenomics

journal_title

Pharmacogenomics

authors

Yen-Revollo JL,Auman JT,McLeod HL

doi

10.2217/14622416.9.11.1639

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

1639-45

issue

11

eissn

1462-2416

issn

1744-8042

journal_volume

9

pub_type

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