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

F Aminkeng; C J D Ross; S R Rassekh; L R Brunham; J Sistonen; M-P Dube; M Ibrahim; T B Nyambo; S A Omar; A Froment; J-M Bodo; S Tishkoff; B C Carleton; M R Hayden; Canadian Pharmacogenomics Network for Drug Safety Consortium

doi:10.1038/tpj.2013.13

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

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

Authors

Collaborators

Canadian Pharmacogenomics Network for Drug Safety Consortium:
Michael Hayden, Bruce Carleton, Colin Ross, Stuart MacLeod, Wyeth Wasserman, Craig Mitton, Anne Smith, Claudette Hildebrand, Lucila Castro Pastrana, Reza Ghannadan, Rod Rassekh, Jonathan Lim, Fudan Miao, Henk Visscher, Kusala Pussegoda, Folefac Aminkeng, Michelle Higginson, Nasim Massah, Mojgan Yazdanpanah, Johanne Sistonen, Ricardo Jimenez, Adrienne Borrie, Ursula Amstutz, Shevaun Hughes, Kaitlyn Shaw, Cheri Nijssen-Jordan, David Johnson, Linda Verbeek, Rick Kaczowka, Patti Stevenson, Andrea Hurton, Paul Grundy, Kent Stobart, Bev Wilson, Sunil Desai, Maria Spavor, Linda Churcher, Terence Chow, Kevin Hall, Nick Honcharik, Sara Israels, Shanna Chan, Byron Garnham, Michelle Staub, Michael Rieder, Becky Malkin, Carol Portwine, Amy Cranston, Gideon Koren, Shinya Ito, Paul Nathan, Mark Greenberg, Facundo Garcia Bournissen, Miho Inoue, Sachi Sakaguchi, Toshihiro Tanaka, Hisaki Fujii, Mina Ogawa, Ryoko Ingram, Taro Kamiya, Smita Karande, Mariana Silva, Stephanie Willing, Regis Vaillancourt, Pat Elliott-Miller, Donna Johnston, Herpreet Mankoo, Elaine Wong, Brenda Wilson, Lauren O'Connor, Maurica Maher, Jean-Francois Bussieres, Denis Lebel, Pierre Barret, Aurelie Closon, Eve Coulson, Marie-Pierre Dube, Michael Phillips, Nada Jabado, Anelise Espirito Santo, Martine Nagy, Denise Avard, Margaret Murray, Darlene Boliver, Marilyn Tiller, Carolanne Osborne

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Acquired Immunodeficiency Syndrome / drug therapy
Acquired Immunodeficiency Syndrome / genetics*
Acquired Immunodeficiency Syndrome / pathology
Black People / genetics
Drug-Related Side Effects and Adverse Reactions / genetics*
Drug-Related Side Effects and Adverse Reactions / pathology
Gene Frequency
Genetic Predisposition to Disease
Genetic Variation
Humans
Neoplasms / drug therapy
Neoplasms / genetics*
Neoplasms / pathology
Polymorphism, Single Nucleotide
Tuberculosis / drug therapy
Tuberculosis / genetics*
Tuberculosis / pathology
White People / genetics

Abstract

Publication types

MeSH terms

Grants and funding