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

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.

UR - https://www.scopus.com/pages/publications/84894487302

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 -