Future Developments

Cross-sectional association studies are a crude method to assess the role of low-penetration genetic traits in polygenic disorders (146), because they are biased by the lack of controls for disease duration, disease expression, and timing of diagnosis. In addition, the overall effect of xenobiotics is determined by the interplay of several genes encoding proteins involved in the multiple pathways of drug metabolism, disposition, and effects. The high degree of complexity and redundancy in the metabolic pathways, combined with the limitations of hypothesis-driven research, may delay the discovery of novel pathways (147). Therefore, more comprehensive pharmacogenomic studies are required to define traits that are determined by multiple polymorphic genes. The Human Genome Project, coupled with DNA array technology, high-throughput screening systems, and advanced bioinformatics may allow rapid elucidation of the complex genetic components of human disease and drug response (1). In contrast to the candidate gene approach, a new pharmacogenomic paradigm is emerging in which the entire human genome is screened for SNPs that may be associated with drug response (148). SNP maps could be used to correlate genetic information with the response to a drug. It would thus not be necessary to identify actual genes involved in determining the response to a drug, but the pattern of SNP markers would suffice (149). The hypothesis-free approach to pharmacogenomics may also allow the identification of new drug targets for further exploration.

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