A single-nucleotide polymorphism tagging set for human drug metabolism and transport.
Interindividual variability in drug response, ranging from no therapeutic benefit to life-threatening adverse reactions, is influenced by variation in genes that control the absorption, distribution, metabolism and excretion of drugs. We genotyped 904 single-nucleotide polymorphisms (SNPs) from 55 such genes in two population samples (European and Japanese) and identified a set of tagging SNPs that represents the common variation in these genes, both known and unknown. Extensive empirical evaluations, including a direct assessment of association with candidate functional SNPs in a new, larger population sample, validated the performance of these tagging SNPs and confirmed their utility for linkage-disequilibrium mapping in pharmacogenetics. The analyses also suggest that rare variation is not amenable to tagging strategies.
Ahmadi
Kourosh R
KR
Department of Biology (Galton Lab), University College London, The Darwin Building, Gower Street, London WC1E 6BT, UK.
Weale
Mike E
ME
Xue
Zhengyu Y
ZY
Soranzo
Nicole
N
Yarnall
David P
DP
Briley
James D
JD
Maruyama
Yuka
Y
Kobayashi
Mikiro
M
Wood
Nicholas W
NW
Spurr
Nigel K
NK
Burns
Daniel K
DK
Roses
Allen D
AD
Saunders
Ann M
AM
Goldstein
David B
DB
D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D020641:Polymorphism, Single Nucleotide
D004364:Pharmaceutical Preparations; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System