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

Recognition that there is a vast quantity of human genetic variation has ha d a pervasive impact on modern medicine, facilitating the identification of scores of genes that underlie monogenic clinical disorders, as well as gen es involved in complex disease processes. The next logical step for human g enetics is the exploration and elucidation of genes involved in differentia l pharmacological response: responders, nonresponders, and those with adver se side effects. An understanding of the role that genes have in pharmacolo gical 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 disc overy and development. To realize the potential of these efforts, it will b e necessary to incorporate a better understanding of the population genetic and evolutionary processes that have shaped genetic variation in modern hu mans. This article introduces these concepts to provide context and guideli nes for the use of this variation (primarily single-nucleotide polymorphism s and haplotypes) in pharmacogenetics.