The Role of Genetic Polymorphisms in Environmental Health. (Research Review)

By Kelada, Samir N.; Eaton, David L. et al. | Environmental Health Perspectives, June 15, 2003 | Go to article overview

The Role of Genetic Polymorphisms in Environmental Health. (Research Review)


Kelada, Samir N., Eaton, David L., Wang, Sophia S., Rothman, Nathaniel R., Khoury, Muin J., Environmental Health Perspectives


Interest is increasing in the role of variations in the human genome (polymorphisms) in modifying the effect of exposures to environmental health hazards (often referred to as gene-environment interaction), which render some individuals or groups in the population more or less likely to develop disease after exposure. This review is intended for an audience of environmental health practitioners and students and is designed to raise awareness about this rapidly growing field of research by presenting established and novel examples of gene-environment interaction that illustrate the major theme of effect modification. Current data gaps are identified and discussed to illustrate limitations of past research and the need for the application of more robust methods in future research projects. Two primary benefits of incorporating genetics into the existing environmental health research framework are illustrated: a) the ability to detect different levels of risk within the population, and b) greater understanding of etiologic mechanisms. Both offer opportunities for developing new methods of disease prevention. Finally, we describe a basic framework for researchers interested in pursuing health effects research that incorporates genetic polymorphisms. Key words: disease susceptibility, environmental health, genetics, polymorphism. Environ Health Perspect 111:1055-1064 (2003). doi:10.1289/ehp.6065 available via http://dx.doi.org/[Online 24 April 2003]

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With the initial completion of the first draft of the human genome sequence (Lander et al. 2001; Venter et al. 2001), interest has dramatically increased in the role of genetics as a determinant of health. Progress in incorporating genetics into public health research has been steady over the last several years, relying mainly on the tools of genetic and molecular epidemiology. Research exploring the role of genetics in determining susceptibility to environmentally induced disease has also grown. The recent abundance of epidemiologic research examining associations between polymorphic genes that code for enzymes involved in xenobiotic biotransformation and disease has on occasion generated interesting findings. However, the approach used in these studies differs substantially from that of traditional environmental health science research. Whereas traditional environmental health sciences seek to understand the effect of exposure of a homogeneous population to some agent, many of the recent genetic and molecular epidemiologic studies have been structured to analyze gene-disease associations, regardless of exposure. In addition, many of the findings have not been replicated in subsequent studies, casting doubt on their validity and leaving the environmental health community with uncertain results with which to proceed.

In this review, we present a general introduction of this evolving area of research on gene-environment interactions for environmental health practitioners and students. We begin by assessing the integration of genetics into environmental health research using the same exposure [right arrow] disease paradigm traditionally used by environmental health scientists, adding genetics to the existing paradigm as a potential modifier of dose or effect of the initial exposure. Then we discuss selected examples of gene-environment interaction from the literature, classifying them into one of three categories on the basis of evidence from laboratory and epidemiologic data. Finally, we describe the benefits of applying this model to future research efforts, and we offer a basic framework for investigators wishing to pursue this type of endeavor.

Environmental Exposures and Human Genetic Variation

Much of the impetus for this area of research has come from pharmacogenetics, which is concerned primarily with the study of genetic variation in drug efficacy and toxicity. It has been recognized for many decades that individual differences in response to pharmacologic treatment, exhibited as drug toxicity or a lack of therapeutic effect, are often caused by genetic differences that result in altered rates of biotransformation (metabolism). …

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