Single-nucleotide polymorphisms, haplotypes, and their relevance to pharmacogenetics

Recognition that there is a vast quantity of human genetic variation has had a pervasive impact on modern medicine, facilitating the identification of scores of genes that underlie monogenic clinical disorders, as well as genes involved in complex disease processes. The next logical step for human genetics is the exploration and elucidation of genes involved in differential pharmacological response: responders, nonresponders, and those with adverse side effects. An understanding of the role that genes have in pharmacological response is the cornerstone of personalized medicine. Pharmacogenetic activities have swiftly embraced these tenets, leading to a proliferation of resources and approaches meant to enable and expedite targeted drug discovery and development. To realize the potential of these efforts, it will be necessary to incorporate a better understanding of the population genetic and evolutionary processes that have shaped genetic variation in modern humans. This article introduces these concepts to provide context and guidelines for the use of this variation (primarily single-nucleotide polymorphisms and haplotypes) in pharmacogenetics.