The Rationale and Aims of Pharmacogenetics

Establishment of definable end-points for the investigation of specific differences between normal and abnormal responders poses another problem. Consider the evaluation of drug treatment of hypertension as a case in point. In this instance, the definitive end-point would be measured by the difference in the incidence of strokes and cardiovascular disease between normal and abnormal drug responders, but this would probably occur years after the trait is recognized and modifying treatment undertaken. Another example of pharmacogenetic interest 

Investigations with more limited goals designed to measure intermediate or short-term changes in biochemical and molecular markers may lessen some of these difficulties. Biological markers that can detect early and subtle differences in individual response would be necessary for this purpose. The most suitable are markers that can be detected in small samples of tissue or body fluids that are accessible to sampling they should be expressed differentially in accordance with differences observed in normal and abnormal responders and they should have a low probability of spontaneous change. 

An important goal of studies with intermediate- and short-term biomarkers is validation of the markers by demonstrating their correlation with definitive endpoints. It is reasonable to expect that these biomarkers will enable differences in human susceptibilities to exogenous chemicals to be detected, or suspected, at an early stage of exposure, and the liability of susceptible persons to be predicted long before the definitive endpoint is reached. It follows that studies using such biomarkers could be accomplished in a much shorter time and at a much lower cost than those aimed at determining definitive end-points. 

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