title: Higher frequency of genetic variants conferring increased risk for ADRs for commonly used drugs treating cancer, AIDS and tuberculosis in persons of African descent.
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.
authors.affiliation: Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: F
authors.initials: F
authors.lastname: Aminkeng
authors.affiliation: Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: C J D
authors.initials: CJ
authors.lastname: Ross
authors.affiliation: Division of Pediatric Hematology/Oncology/BMT, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: S R
authors.initials: SR
authors.lastname: Rassekh
authors.affiliation: 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.
authors.forename: L R
authors.initials: LR
authors.lastname: Brunham
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Sistonen
authors.affiliation: Montreal Heart Institute Research Centre and Universite de Montreal, Montreal, Quebec, Canada.
authors.forename: M-P
authors.initials: MP
authors.lastname: Dube
authors.affiliation: Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
authors.forename: M
authors.initials: M
authors.lastname: Ibrahim
authors.affiliation: Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors.forename: T B
authors.initials: TB
authors.lastname: Nyambo
authors.affiliation: Kenya Medical Research Institute, Center for Biotechnology Research and Development, Nairobi, Kenya.
authors.forename: S A
authors.initials: SA
authors.lastname: Omar
authors.affiliation: UMR 208, IRD-MNHN, Musée de l'Homme, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Froment
authors.affiliation: Ministère de la Recherche Scientifique et de l'Innovation, Yaoundé, Cameroon.
authors.forename: J-M
authors.initials: JM
authors.lastname: Bodo
authors.affiliation: Departments of Genetics and Biology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tishkoff
authors.affiliation: Division of Translational Therapeutics, Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: B C
authors.initials: BC
authors.lastname: Carleton
authors.affiliation: 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.
authors.forename: M R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D044383:Black People / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D014376:Tuberculosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D044465:White People / Q000235:genetics