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Med Clin North Am. 2005 Jul;89(4):721-38.

Health-related disparities: influence of environmental factors.

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National Institute of Environmental Health Sciences, United States Department of Health and Human Services, National Institutes of Health, PO Box 12233, Research Triangle Park, NC 27709, USA.


Racial disparities in health cannot be explained solely on the basis of poverty, access to health care, behavior, or environmental factors. Their complex etiology is dependent on interactions between all these factors plus genetics. Scientists have been slow to consider genetics as a risk factor because genetic polymorphisms tend to be more variable within a race than between races. Now that studies are demonstrating the existence of racial differences in allelic frequencies for multiple genes affecting a single biologic mechanism, the present argument for a significant genetic role in contributing to health disparities is gaining support. Individuals vary, often significantly, in their response to environmental agents. This variability provides a high "background noise" when scientists examine human populations to identify environmental links to disease. This variability often masks important environmental contributors to disease risk and is a major impediment to efforts to investigate the causes of diseases.Fortunately, investments in the various genome projects have led to the development of tools and databases that can be used to help identify the genetic variations in environmental response genes that can lead to such wide differences in disease susceptibility. NIEHS developed the environ-mental genome project to catalog these genetic variants (polymorphisms)and to identify the ones that play a major role in human susceptibility to environmental agents. This information is being used in epidemiologic studies to pinpoint environmental contributors to disease better. The research summarized in this article is critically important for tying genetics and the environment to health disparities, and for the development of a rational approach to gauge environmental threats. Common variants in genes play pivotal roles in determining if or when illness or death result from exposure to drugs or environmental xenobiotics. Most common variants exist in all human populations, but their frequency can vary substantially,rendering individuals or groups more or less susceptible to particular environmental exposures. Such findings are consistent with the highly publicized analogy, "genetics loads the gun, but the environment pulls the trigger." That is, one can inherit the genetic predisposition to develop a disease but will do so only if or when exposed to the environmental trigger. Poor people have approximately the same genetic makeup as everyone else,but they have the unfortunate experience of living and working in environments containing multiple and high levels of carcinogens or other toxicants capable of interacting with susceptibility genes to cause disease.Furthermore, certain disadvantaged ethnic groups may have a higher incidence of certain susceptible genes that render them more vulnerable to adverse effects of the environments they inhabit. For both of these reasons,much of the nation's disease burden could likely be reduced through better environmental protection practices, especially in low-income and minority communities. Of the many implications of polymorphisms and frequency variations for public health and the practice of medicine, however, none is more urgent than the choice of drugs in therapy. Using such knowledge,randomized trials have identified race-specific drug response differences between blacks and whites [42].To date, most knowledge of the health effects of environmental factors is derived from studies of single agents. The reality, though, is that environmental contributions to health disparities are mostly from multiple agents. These simultaneous exposures to multiple risk factors, which may accumulate or interact synergistically, remain to be fully explained and defined.Finally, health disparity is a significant public health problem that cannot be solved using "business as usual" approaches for funding and priority setting. The current emphasis on basic and clinical research at the exclusion of public health and the social sciences does not provide the interdisciplinary research teams necessary to address such a complex problem as health disparities. Although the poor will always be with us, their health could be greatly improved if social, environmental, and genetic scientists could find ways to collaborate and develop more insightful and relevant ways to address the health of disadvantaged communities.

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