title: Criteria for the selection of single nucleotide polymorphisms in pathway pharmacogenetics: TNF inhibitors as a case study.
abstract: Pharmacogenetics aims to identify genetic variation to predict drug response or to establish an individual optimal dose. Classically, explorative pharmacogenetic studies are performed concerning a limited number of SNPs in genes encoding enzymes involved in the drug's metabolic route. Alternatively, potential markers across the genome are elucidated by the performance of the hypothesis-free genome-wide method. Besides their successful use, both methods provide substantial disadvantages. A solution toward these difficulties is the pathway pharmacogenetic approach, which considers variability in the entire pathway without restricting the analysis to only one gene. In this article, we present selection criteria for this approach to effectively explore potential associating SNPs. As an illustration, the method is applied to the biological adalimumab as a case study.
authors.affiliation: Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Wouter M
authors.initials: WM
authors.lastname: Kooloos
authors.forename: Judith A M
authors.initials: JA
authors.lastname: Wessels
authors.forename: Tahar
authors.initials: T
authors.lastname: van der Straaten
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: Henk-Jan
authors.initials: HJ
authors.lastname: Guchelaar
mesh_terms: D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D010597:Pharmacogenetics / Q000379:methods* / Q000592:standards*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D018124:Receptors, Tumor Necrosis Factor; D000068879:Adalimumab