Format

Send to

Choose Destination
See comment in PubMed Commons below
Pharmacogenomics J. 2014 Dec;14(6):555-63. doi: 10.1038/tpj.2014.22. Epub 2014 May 27.

Pharmacogenomic diversity in Singaporean populations and Europeans.

Author information

1
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.
2
Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research, Singapore.
3
Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
4
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
5
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.
6
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.
7
Health Sciences Authority, Singapore.
8
Department of Pharmacology, National University of Singapore, Singapore.
9
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.
10
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.
11
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.
12
1] Health Sciences Authority, Singapore [2] Duke-NUS Graduate Medical School, Singapore.
13
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.

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.

PMID:
24861855
DOI:
10.1038/tpj.2014.22
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center