The Role and Impact of SNPs in Pharmacogenomics and Personalized Medicine

Rachel      E. Laing; Patricia      Hess; Yingjie      Shen; Jian      Wang; Sean      X. Hu

Abstract

Over 10 million SNPs have been discovered to date as the result of both a private and public effort in the past two decades. Extensive investigations on SNPs have been performed to assess clinical applications for pharmacogenomics and Personalized Medicine. Recently, around the 10th anniversary of the first publication by the Human Genome Project, Hamburg and Collins addressed questions regarding the progress of the genomics field and its impact on pharmacogenomics / Personalized Medicine. Similar questions remain around the potential link of SNPs to Personalized Medicine applications, and the extent to which they have impacted “real world” clinical practices. Built upon these previous efforts, and to achieve our objectives of describing and assessing the role of SNPs and their impact on Personalized Medicine, this article analyzes and summarizes the clinical relevance, molecular mechanisms, clinical evidence, and preliminary regulatory and clinical guideline information of relevant SNPs. In addition, it focuses on two applications directly related to Personalized Medicine drug therapeutics: predictive biomarkers for patient stratification and dose selection. In summary, this article attempts to provide a general and comprehensive view of the role of SNPs in pharmacogenomics and Personalized Medicine, as well as a practical view of their impact on clinical practice today.

Keywords: Biomarker, Cytochrome P450, HLA, Single Nucleotide Polymorphism, Pharmacogenomics, Stratified Medicine, Personalized Medicine Therapeutics, Personalized Medicine, Imipramine, Nortriptyline, Atomoxetine, Sulphonylureas