摘要：Objectives. Pharmacogenetic research and clinical testing raise important concerns for individuals and communities, especially where past medical research and practice has perpetrated harm and cultivated distrust of health care systems and clinicians. We investigated perceptions of pharmacogenetics among Alaska Native (AN) people. Methods. We held four focus groups for 32 ANs in south central Alaska to elicit views about pharmacogenetics in general and for treatment of cardiovascular disease, breast cancer, depression, and nicotine addiction. We analyzed data for perceived risks and rewards of pharmacogenetics. Results. Potential risks of pharmacogenetics included health care rationing, misuse of information, and stigma to individuals and the AN community. Potential rewards included decreased care costs, improved outcomes, and community development. Participants also discussed 8 contingent conditions that could mitigate risks and increase pharmacogenetic acceptability. Conclusions. Alaska Natives perceive pharmacogenetics as potentially benefitting and harming individuals, communities, and health systems, depending on methods and oversight. Researchers, clinicians, and administrators, especially in community-based clinic and health care systems serving minority populations, must address this “double-edged sword” to effectively conduct pharmacogenetics. References to “personalized” and “individualized” medicine are now frequently made in popular and professional health media, with particular emphasis on the potential of pharmacogenetic research and clinical testing to ensure safer and more effective drug therapy. Such benefits could have an important impact; adverse effects from pharmacologic agents and drug reactions result in more than 100 000 deaths annually in the United States 1,2 and contribute significantly to health care costs. 3–6 Accurate use of pharmacogenetics requires knowledge of genetic variation from diverse populations because genetic differences across groups can affect both dosing requirements and likelihood of adverse drug reactions for a number of drugs. 1,4,7 However, most pharmacogenetic research has been done in populations of European descent. 7 Scant data exist for American Indian and Alaska Native (AI/AN) populations, making it difficult to assess the clinical utility of pharmacogenetics for AI/AN individuals. 8 In addition, the cost of pharmacogenetic testing may remain out of reach of underresourced health systems such as Medicaid, the Indian Health Service, or other tribal health systems. Under this scenario, the net effect of pharmacogenetics could increase, rather than decrease, health disparities. For the AN people, considerations about participation in pharmacogenetics must be understood in the context of a documented history of unethical, even harmful, research conducted in their communities and the accumulation of associated distrust of outside researchers. Examples include the Barrow Alaska Alcohol study, research with the Havasupai Tribe in Arizona, and related concerns of the Navajo Nation that led to a moratorium on genetic research that continues today. 9–12 Mistrust of medical care endures because of negative experiences with the Indian Health Service and the lack of cultural knowledge of clinicians. These concerns raise timely and relevant questions for medical and tribal communities regarding the potential value and consequences of pharmacogenetics in indigenous communities across North America. 13–15 We aimed to understand the key concerns and priorities of the AN people regarding the use of pharmacogenetics in Alaska’s tribal health care system. We conducted research in a tribally owned and managed health care organization to engage AN community perspectives and to inform administrative and clinical decisions regarding use of pharmacogenetics in 4 clinical and 2 research scenarios. 16 This community-based participatory research approach offered a model for investigating the acceptability of pharmacogenetics in other AN and American Indian health systems, and in systems serving other populations with histories of negative experiences with medical research and care. 17,18
