title: A bivariate functional mapping model for identifying haplotypes that control drug response for systolic and diastolic blood pressures.
abstract: A bivariate functional mapping model has been proposed to detect haplotype-based DNA sequence variants that regulate the response curves of systolic and diastolic blood pressures (SBP and DBP) to a particular drug. This model capitalizes on the haplotype structure constructed by single nucleotide polymorphisms (SNPs) and incorporates the mathematical aspects of pharmacodynamic reactions into the estimation process, aimed to identify DNA sequence variants responsible for drug response. In this way, by estimating and testing the curve parameters that define drug response, many genetically and clinically meaningful hypotheses regarding the degree and pattern of the genetic control of SBP and DBP can be formulated, tested and disseminated. In a pharmacogenetic study composed of 107 subjects, our bivariate model has probed two haplotypes within the beta 2AR candidate gene that exert a significant effect on both SBP and DBP respond to dobutamine. With this candidate gene, two SNPs are genotyped, with allele Gly16 (G) and Arg16 (A) at codon 16 and alleles Glu27 (G) and Gln27 (C) at codon 27, respectively. The significant haplotypes are [AC] for SBP and [GG] for DBP. This model provides a powerful tool for elucidating the genetic variants of drug response and ultimately designing personalized medications based on each patient's genetic makeup.
authors.affiliation: Duke University, Department of Biostatistics and Bioinformatics, Duke Clinical Research Institute, P.O. Box 17969, Durham, NC 27715, USA. annie.lin@duke.edu
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.forename: Rongling
authors.initials: R
authors.lastname: Wu
authors.forename: Julie
authors.initials: J
authors.lastname: Johnson
mesh_terms: D000465:Algorithms; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D019295:Computational Biology; D004247:DNA / Q000235:genetics; D003971:Diastole / Q000187:drug effects / Q000235:genetics; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D008957:Models, Genetic; D015233:Models, Statistical; D010597:Pharmacogenetics / Q000706:statistics & numerical data*; D013599:Systole / Q000187:drug effects / Q000235:genetics
chemical_list: D004247:DNA