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Pharmacogenomics J. 2014 Apr;14(2):160-70. doi: 10.1038/tpj.2013.13. Epub 2013 Apr 16.

Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent.

Author information

1
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
2
Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
3
Division of Pediatric Hematology/Oncology/BMT, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
4
1] Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada [2] Translational Laboratory in Genetic Medicine, Department of Medicine, National University of Singapore and Association for Science, Technology and Research (A*STAR), Singapore.
5
1] Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada [2] Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland.
6
Montreal Heart Institute Research Centre and Universite de Montreal, Montreal, Quebec, Canada.
7
Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
8
Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
9
Kenya Medical Research Institute, Center for Biotechnology Research and Development, Nairobi, Kenya.
10
UMR 208, IRD-MNHN, Musée de l'Homme, Paris, France.
11
Ministère de la Recherche Scientifique et de l'Innovation, Yaoundé, Cameroon.
12
Departments of Genetics and Biology, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

There is established clinical evidence for differences in drug response, cure rates and survival outcomes between different ethnic populations, but the causes are poorly understood. Differences in frequencies of functional genetic variants in key drug response and metabolism genes may significantly influence drug response differences in different populations. To assess this, we genotyped 1330 individuals of African (n=372) and European (n=958) descent for 4535 single-nucleotide polymorphisms in 350 key drug absorption, distribution, metabolism, elimination and toxicity genes. Important and remarkable differences in the distribution of genetic variants were observed between Africans and Europeans and among the African populations. These could translate into significant differences in drug efficacy and safety profiles, and also in the required dose to achieve the desired therapeutic effect in different populations. Our data points to the need for population-specific genetic variation in personalizing medicine and care.

PMID:
23588107
PMCID:
PMC4684079
DOI:
10.1038/tpj.2013.13
[Indexed for MEDLINE]
Free PMC Article

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