title: Added value of pharmacogenetic testing in predicting statin response: results from the REGRESS trial.
abstract: It was investigated whether pharmacogenetic factors, both as single polymorphism and as gene-gene interactions, have an added value over non-genetic factors in predicting statin response. Five common polymorphisms were selected in apolipoprotein E, angiotensin-converting enzyme, hepatic lipase and toll-like receptor 4. Linear regression models were built and compared on R(2) to estimate the added value of single polymorphisms and gene-gene interactions. The selected polymorphisms and the gene-gene interactions had a small added value in predicting change in low-density lipoprotein cholesterol levels (LDL-c) as response to statins over the non-genetic predictors (P=0.104), and also in predicting LDL-c in non-treated patients (P=0.016). Moreover, four gene-gene interactions with statin therapy were identified. The added value of genetic factors over non-genetic variables is for the greater part produced by gene-gene interactions. This underlines the importance to examine gene-gene interactions in future (pharmaco)genetic research.
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. f.vanderbaan@umcutrecht.nl
authors.forename: F H
authors.initials: FH
authors.lastname: van der Baan
authors.forename: M J
authors.initials: MJ
authors.lastname: Knol
authors.forename: A H
authors.initials: AH
authors.lastname: Maitland-van der Zee
authors.forename: J J
authors.initials: JJ
authors.lastname: Regieli
authors.forename: E P A
authors.initials: EP
authors.lastname: van Iperen
authors.forename: A C G
authors.initials: AC
authors.lastname: Egberts
authors.forename: O H
authors.initials: OH
authors.lastname: Klungel
authors.forename: D E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: J W
authors.initials: JW
authors.lastname: Jukema
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage; D001057:Apolipoproteins E / Q000235:genetics*; D054316:Biomarkers, Pharmacological; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D004843:Epistasis, Genetic; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008049:Lipase / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011237:Predictive Value of Tests; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D000596:Amino Acids; D001057:Apolipoproteins E; D054316:Biomarkers, Pharmacological; D008078:Cholesterol, LDL; C504173:LIPC protein, human; D051197:Toll-Like Receptor 4; D008049:Lipase; D007703:Peptidyl-Dipeptidase A; C013165:statine