Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events

M. Leusink; N. C. Onland-Moret; F. W. Asselbergs; B. Ding; S. Kotti; N. R. van Zuydam; A. C. Papp; N. Danchin; L. Donnelly; A. D. Morris; D. I. Chasman; P. A. F. M. Doevendans; O. H. Klungel; P. M. Ridker; W. H. van Gilst; T. Simon; F. Nyberg; C. N. A. Palmer; W. Sadee; P. van der Harst; P. I. W. de Bakker; A. de Boer; C. Verstuyft; A. H. Maitland-van der Zee

doi:10.1038/clpt.2013.194

Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events

M. Leusink, N. C. Onland-Moret, F. W. Asselbergs, B. Ding, S. Kotti, N. R. van Zuydam, A. C. Papp, N. Danchin, L. Donnelly, A. D. Morris, D. I. Chasman, P. A. F. M. Doevendans, O. H. Klungel, P. M. Ridker, W. H. van Gilst, T. Simon, F. Nyberg, C. N. A. Palmer, W. Sadee, P. van der HarstP. I. W. de Bakker, A. de Boer, C. Verstuyft, A. H. Maitland-van der Zee (Lead / Corresponding author)

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Abstract

The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta-analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single-nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta-analysis of statin × SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 × 10) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.Clinical Pharmacology & Therapeutics (2013); advance online publication 30 October 2013. doi:10.1038/clpt.2013.194.

Original language	English
Pages (from-to)	314-320
Number of pages	7
Journal	Clinical Pharmacology & Therapeutics
Volume	95
Issue number	3
DOIs	https://doi.org/10.1038/clpt.2013.194
Publication status	Published - Mar 2014

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Leusink, M., Onland-Moret, N. C., Asselbergs, F. W., Ding, B., Kotti, S., van Zuydam, N. R., Papp, A. C., Danchin, N., Donnelly, L., Morris, A. D., Chasman, D. I., Doevendans, P. A. F. M., Klungel, O. H., Ridker, P. M., van Gilst, W. H., Simon, T., Nyberg, F., Palmer, C. N. A., Sadee, W., ... Maitland-van der Zee, A. H. (2014). Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events. Clinical Pharmacology & Therapeutics, 95(3), 314-320. https://doi.org/10.1038/clpt.2013.194

@article{dc463c367c5f454989ed785a1b509276,

title = "Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events",

abstract = "The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta-analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single-nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta-analysis of statin × SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 × 10) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.Clinical Pharmacology & Therapeutics (2013); advance online publication 30 October 2013. doi:10.1038/clpt.2013.194.",

author = "M. Leusink and Onland-Moret, {N. C.} and Asselbergs, {F. W.} and B. Ding and S. Kotti and {van Zuydam}, {N. R.} and Papp, {A. C.} and N. Danchin and L. Donnelly and Morris, {A. D.} and Chasman, {D. I.} and Doevendans, {P. A. F. M.} and Klungel, {O. H.} and Ridker, {P. M.} and {van Gilst}, {W. H.} and T. Simon and F. Nyberg and Palmer, {C. N. A.} and W. Sadee and {van der Harst}, P. and {de Bakker}, {P. I. W.} and {de Boer}, A. and C. Verstuyft and {Maitland-van der Zee}, {A. H.}",

year = "2014",

month = mar,

doi = "10.1038/clpt.2013.194",

language = "English",

volume = "95",

pages = "314--320",

journal = "Clinical Pharmacology & Therapeutics",

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Leusink, M, Onland-Moret, NC, Asselbergs, FW, Ding, B, Kotti, S, van Zuydam, NR, Papp, AC, Danchin, N, Donnelly, L, Morris, AD, Chasman, DI, Doevendans, PAFM, Klungel, OH, Ridker, PM, van Gilst, WH, Simon, T, Nyberg, F, Palmer, CNA, Sadee, W, van der Harst, P, de Bakker, PIW, de Boer, A, Verstuyft, C & Maitland-van der Zee, AH 2014, 'Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events', Clinical Pharmacology & Therapeutics, vol. 95, no. 3, pp. 314-320. https://doi.org/10.1038/clpt.2013.194

TY - JOUR

T1 - Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events

AU - Leusink, M.

AU - Onland-Moret, N. C.

AU - Asselbergs, F. W.

AU - Ding, B.

AU - Kotti, S.

AU - van Zuydam, N. R.

AU - Papp, A. C.

AU - Danchin, N.

AU - Donnelly, L.

AU - Morris, A. D.

AU - Chasman, D. I.

AU - Doevendans, P. A. F. M.

AU - Klungel, O. H.

AU - Ridker, P. M.

AU - van Gilst, W. H.

AU - Simon, T.

AU - Nyberg, F.

AU - Palmer, C. N. A.

AU - Sadee, W.

AU - van der Harst, P.

AU - de Bakker, P. I. W.

AU - de Boer, A.

AU - Verstuyft, C.

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

PY - 2014/3

Y1 - 2014/3

N2 - The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta-analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single-nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta-analysis of statin × SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 × 10) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.Clinical Pharmacology & Therapeutics (2013); advance online publication 30 October 2013. doi:10.1038/clpt.2013.194.

AB - The association of nonfunctional variants of the cholesteryl ester transfer protein (CETP) with efficacy of statins has been a subject of debate. We evaluated whether three functional CETP variants influence statin efficacy. The effect of CETP genotype on achieved levels of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total cholesterol during statin treatment was estimated by meta-analysis of the linear regression outcomes of three studies (11,021 individuals). The effect of these single-nucleotide polymorphisms (SNPs) on statin response in protecting against myocardial infarction (MI) was estimated by meta-analysis of statin × SNP interaction terms from logistic regression in five studies (16,570 individuals). The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T allele (P = 6 × 10) and reduced protection against MI by statins (interaction odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP variants, we showed that in carriers of the rs3764261 T variant, HDLc increased more during statin treatment, and protection against MI by statins appeared to be reduced as compared with those in noncarriers.Clinical Pharmacology & Therapeutics (2013); advance online publication 30 October 2013. doi:10.1038/clpt.2013.194.

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U2 - 10.1038/clpt.2013.194

DO - 10.1038/clpt.2013.194

M3 - Article

SN - 0009-9236

VL - 95

SP - 314

EP - 320

JO - Clinical Pharmacology & Therapeutics

JF - Clinical Pharmacology & Therapeutics

IS - 3

ER -

Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on cholesterol levels and cardiovascular events

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