P450 Pharmacogenetics in Indigenous North American Populations

Lindsay Henderson,Renee Robinson,Katrina Claw,Erica Woodahl,Bert Boyer,Kenneth Thummel,Wylie Burke

doi:10.3390/jpm8010009

Abstract

Indigenous North American populations, including American Indian and Alaska Native peoples in the United States, the First Nations, Métis and Inuit peoples in Canada and Amerindians in Mexico, are historically under-represented in biomedical research, including genomic research on drug disposition and response. Without adequate representation in pharmacogenetic studies establishing genotype-phenotype relationships, Indigenous populations may not benefit fully from new innovations in precision medicine testing to tailor and improve the safety and efficacy of drug treatment, resulting in health care disparities. The purpose of this review is to summarize and evaluate what is currently known about cytochrome P450 genetic variation in Indigenous populations in North America and to highlight the importance of including these groups in future pharmacogenetic studies for implementation of personalized drug therapy.

Highlights

Pharmacogenetics, a form of genomic medicine, aims to establish how genetic variation can affect an individual’s response to drugs, guiding the selection of the best drug and dose for a patient to improve healthcare quality [1]
This review focuses on what is currently known about P450 pharmacogenetics in Indigenous North American populations and how the unique variation found in these populations may impact drug metabolism and response
The primary focusenzymes, of this review is to provide a summary and of thephenotyping, P450 pharmacogenetic research conclusions fromwith theand study

Summary

Introduction

Pharmacogenetics, a form of genomic medicine, aims to establish how genetic variation can affect an individual’s response to drugs, guiding the selection of the best drug and dose for a patient to improve healthcare quality [1]. The field of pharmacogenetics has the potential to improve health outcomes and reduce the cost of care by maximizing therapeutic success and minimizing the risk of adverse drug reactions or therapeutic failure at the population and potentially the individual level. A major issue in the translation of pharmacogenetic research into clinical practice is that existing databases have been populated from studies that lack significant ethnic and racial diversity. Diversity in genomic research, including pharmacogenetics, has increased in recent years, oversampling of populations of European ancestry continues to be a problem in the field. The latest analysis of genome-wide association studies found that 81% of samples were from individuals of European ancestry [2].

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Conclusion