title: Pharmacogenomic diversity in Singaporean populations and Europeans.
abstract: Differences in the frequency of pharmacogenomic variants may influence inter-population variability in drug efficacy and risk of adverse drug reactions (ADRs). We investigated the diversity of ∼ 4500 genetic variants in key drug-biotransformation and -response genes among three South East Asian populations compared with individuals of European ancestry. We compared rates of reported ADRs in these Asian populations to determine if the allelic differentiation corresponded to an excess of the associated ADR. We identified an excess of ADRs related to clopidogrel in Singaporean Chinese, consistent with a higher frequency of a known risk variant in CYP2C19 in that population. We also observed an excess of ADRs related to platinum compounds in Singaporean CHS, despite a very low frequency of known ADR risk variants, suggesting the presence of additional genetic and non-genetic risk factors. Our results point to substantial diversity at specific pharmacogenomic loci that may contribute to inter-population variability in drug response phenotypes.
authors.affiliation: 1] Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore [2] Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore [3] Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: L R
authors.initials: LR
authors.lastname: Brunham
authors.affiliation: Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore.
authors.forename: S L
authors.initials: SL
authors.lastname: Chan
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: R
authors.initials: R
authors.lastname: Li
authors.affiliation: Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Aminkeng
authors.affiliation: 1] Saw Swee Hock School of Public Health, National University of Singapore, Singapore [2] NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore.
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: W Y
authors.initials: WY
authors.lastname: Saw
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: R T H
authors.initials: RT
authors.lastname: Ong
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: E N
authors.initials: EN
authors.lastname: Pillai
authors.affiliation: 1] Division of Translational Therapeutics, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada [2] Pharmaceutical Outcomes Programme, BC Children's Hospital, Vancouver, BC, Canada.
authors.forename: B C
authors.initials: BC
authors.lastname: Carleton
authors.affiliation: Health Sciences Authority, Singapore.
authors.forename: D
authors.initials: D
authors.lastname: Toh
authors.affiliation: Health Sciences Authority, Singapore.
authors.forename: S H
authors.initials: SH
authors.lastname: Tan
authors.affiliation: Department of Pharmacology, National University of Singapore, Singapore.
authors.forename: S H
authors.initials: SH
authors.lastname: Koo
authors.affiliation: Department of Pharmacology, National University of Singapore, Singapore.
authors.forename: E J D
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: 1] Saw Swee Hock School of Public Health, National University of Singapore, Singapore [2] Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden [3] Center for Molecular Epidemiology, National University of Singapore, Singapore.
authors.forename: K S
authors.initials: KS
authors.lastname: Chia
authors.affiliation: 1] Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada [2] Division of Translational Therapeutics, Department of Pediatrics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: C J D
authors.initials: CJ
authors.lastname: Ross
authors.affiliation: 1] Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore [2] Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
authors.affiliation: 1] Health Sciences Authority, Singapore [2] Duke-NUS Graduate Medical School, Singapore.
authors.forename: C
authors.initials: C
authors.lastname: Sung
authors.affiliation: 1] Saw Swee Hock School of Public Health, National University of Singapore, Singapore [2] NUS Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore [3] Life Sciences Institute, National University of Singapore, Singapore [4] Department of Statistics and Applied Probability, National University of Singapore, Singapore.
authors.forename: Y Y
authors.initials: YY
authors.lastname: Teo
mesh_terms: D001711:Biotransformation; D064420:Drug-Related Side Effects and Adverse Reactions; D005060:Europe; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D012846:Singapore