Added value of pharmacogenetic testing in predicting statin response: Results from the REGRESS trial
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Publication date
2013-08-01
Authors
van der Baan, Frederieke H
Knol, Mirjam J.
Maitland-Van der Zee, Anke-Hilse
Regieli, J.J.
Van Iperen, E.P.A.
Egberts, Antoine
Klungel, Olaf H.
Grobbee, D.E.
Jukema, J.W.
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Article
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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 R2to 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. © 2013 Macmillan Publishers Limited.
Keywords
Gene-gene interactions, Genotype, Pharmacogenetics, Pravastatin response, apolipoprotein E, dipeptidyl carboxypeptidase, liver triacylglycerol lipase, low density lipoprotein cholesterol, placebo, pravastatin, toll like receptor 4, adult, angiotensin converting enzyme gene, apolipoprotein E gene, article, controlled study, coronary artery atherosclerosis, double blind procedure, drug response, female, gene interaction, genetic polymorphism, genetic screening, hepatic lipase gene, heredity, human, major clinical study, male, pharmacogenetics, prediction, priority journal, randomized controlled trial, toll like receptor 4 gene
Citation
Van Der Baan, F H, Knol, M J, Maitland-Van Der Zee, A H, Regieli, J J, Van Iperen, E P A, Egberts, A C G, Klungel, O H, Grobbee, D E & Jukema, J W 2013, 'Added value of pharmacogenetic testing in predicting statin response: Results from the REGRESS trial', The Pharmacogenomics Journal, vol. 13, no. 4, pp. 318-324. https://doi.org/10.1038/tpj.2012.12