Added value of pharmacogenetic testing in predicting statin response: results from the REGRESS trial

F.H. van der Baan; M.J. Knol; A.H. Maitland-van der Zee; J.J. Regieli; E.P. van Iperen; A.C.G. Egberts; O.H. Klungel; D.E. Grobbee; J.W. Jukema

doi:10.1038/tpj.2012.12

Added value of pharmacogenetic testing in predicting statin response: results from the REGRESS trial

F.H. van der Baan, M.J. Knol, A.H. Maitland-van der Zee, J.J. Regieli, E.P. van Iperen, A.C.G. Egberts, O.H. Klungel, D.E. Grobbee, J.W. Jukema

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	318-24
Number of pages	7
Journal	The Pharmacogenomics Journal
Volume	13
Issue number	4
DOIs	https://doi.org/10.1038/tpj.2012.12
Publication status	Published - Aug 2013

Keywords

Amino Acids
Apolipoproteins E
Biomarkers, Pharmacological
Cholesterol, LDL
Epistasis, Genetic
Genotype
Humans
Linear Models
Lipase
Peptidyl-Dipeptidase A
Predictive Value of Tests
Toll-Like Receptor 4
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

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10.1038/tpj.2012.12

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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.",

keywords = "Amino Acids, Apolipoproteins E, Biomarkers, Pharmacological, Cholesterol, LDL, Epistasis, Genetic, Genotype, Humans, Linear Models, Lipase, Peptidyl-Dipeptidase A, Predictive Value of Tests, Toll-Like Receptor 4, Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't",

author = "{van der Baan}, F.H. and M.J. Knol and {Maitland-van der Zee}, A.H. and J.J. Regieli and {van Iperen}, E.P. and A.C.G. Egberts and O.H. Klungel and D.E. Grobbee and J.W. Jukema",

year = "2013",

month = aug,

doi = "10.1038/tpj.2012.12",

language = "English",

volume = "13",

pages = "318--24",

journal = "The Pharmacogenomics Journal",

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T2 - results from the REGRESS trial

AU - van der Baan, F.H.

AU - Knol, M.J.

AU - Maitland-van der Zee, A.H.

AU - Regieli, J.J.

AU - van Iperen, E.P.

AU - Egberts, A.C.G.

AU - Klungel, O.H.

AU - Grobbee, D.E.

AU - Jukema, J.W.

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

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KW - Apolipoproteins E

KW - Biomarkers, Pharmacological

KW - Cholesterol, LDL

KW - Epistasis, Genetic

KW - Genotype

KW - Humans

KW - Linear Models

KW - Lipase

KW - Peptidyl-Dipeptidase A

KW - Predictive Value of Tests

KW - Toll-Like Receptor 4

KW - Clinical Trial

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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DO - 10.1038/tpj.2012.12

M3 - Article

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SN - 1470-269X

VL - 13

SP - 318

EP - 324

JO - The Pharmacogenomics Journal

JF - The Pharmacogenomics Journal

IS - 4

ER -

Added value of pharmacogenetic testing in predicting statin response: results from the REGRESS trial

Abstract

Keywords

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