The Role and Impact of SNPs in Pharmacogenomics and Personalized Medicine

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 10(th) 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.

Molecular diagnostics

“…Pharmacogenomics, a promising area in personalized medicine introduces the concept of molecular markers (biomarkers) to assess drug efficacy, safety and disease risk. 52 It promises to predict the individual outcome of specific therapies in addition to broad pharmacological strategies while considering both host and pathogen to determine the "right drug" for the "right patient" at the "right time". For example individualized antibiotic treatment has already been initiated by considering drug-metabolism enzyme variants.…”

“…51 Moreover, recent studies are extending such treatment by focusing on SNP's, haplotyping, particular gene copy numbers and the individual response of the host's immune system. [52][53][54] Variations in the human multidrug-resistance gene-1 (MDR1) for example, such as a C to T SNP at position 3435, can predict therapy response to highly active antiretroviral therapy (HAART) in HIV-1 patients. 55 Furthermore, although abacavir is an effective treatment for HIV, fatal hypersensitivity reactions have been linked with particular HLA alleles.…”

Fatty Acid Synthesis Pathway Genetic Variants and Clinical Outcome of Non-Small Cell Lung Cancer Patients after Surgery

“…Single nucleotide polymorphism (SNP), a common typical genomic variation, can be used as a stable biomarker of genetic background to predict the risk, therapeutic response and prognosis of cancer (Laing et al, 2011;Liu et al, 2012). Several studies have also discussed the relationship between polymorphisms of DNL genes and development and prognosis of cancers (Nguyen et al, 2010;Eggert et al, 2012).…”

Role of bioinformatics and pharmacogenomics in drug discovery and development process

“…Single nucleotide polymorphisms (SNPs) play a major role in variable drug response. SNPs occur every 100-300 bases along the three-billion-base human genome; therefore, millions of SNPs must be identified and analyzed to determine their involvement (if any) in drug response (Laing et al 2011). Limited awareness and knowledge toward the relationship between gene variants and variable drug response also act as limiting factor to implicate pharmacogenomics-based drug design and delivery process.…”