title: A single-nucleotide polymorphism tagging set for human drug metabolism and transport.
abstract: 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.
authors.affiliation: Department of Biology (Galton Lab), University College London, The Darwin Building, Gower Street, London WC1E 6BT, UK.
authors.forename: Kourosh R
authors.initials: KR
authors.lastname: Ahmadi
authors.forename: Mike E
authors.initials: ME
authors.lastname: Weale
authors.forename: Zhengyu Y
authors.initials: ZY
authors.lastname: Xue
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: David P
authors.initials: DP
authors.lastname: Yarnall
authors.forename: James D
authors.initials: JD
authors.lastname: Briley
authors.forename: Yuka
authors.initials: Y
authors.lastname: Maruyama
authors.forename: Mikiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.forename: Nigel K
authors.initials: NK
authors.lastname: Spurr
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Burns
authors.forename: Allen D
authors.initials: AD
authors.lastname: Roses
authors.forename: Ann M
authors.initials: AM
authors.lastname: Saunders
authors.forename: David B
authors.initials: DB
authors.lastname: Goldstein
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D020641:Polymorphism, Single Nucleotide
chemical_list: D004364:Pharmaceutical Preparations; C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System