High HDL cholesterol does not protect against coronary artery disease when associated with combined cholesteryl ester transfer protein and hepatic lipase gene variants

Abstract Cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are two HDL modifying proteins that have both pro- and anti-atherogenic properties. We hypothesized that CETP and HL synergistically affect HDL cholesterol and atherosclerotic risk. To test our hypothesis, we analysed the gen...

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Bibliographic Details
Published in:Atherosclerosis 2008-09, Vol.200 (1), p.161-167
Main Authors: van Acker, Bernadette A.C, Botma, Gert-Jan, Zwinderman, Aeilko H, Kuivenhoven, Jan Albert, Dallinga-Thie, Geesje M, Sijbrands, Eric J.G, Boer, Jolanda M.A, Seidell, Jacob C, Jukema, J. Wouter, Kastelein, John J.P, Jansen, Hans, Verhoeven, Adrie J.M
Format: Article
Language:English
Subjects:
Aged
Atherosclerosis
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Cardiovascular
Case-Control Studies
Cholesterol Ester Transfer Proteins - blood
Cholesterol Ester Transfer Proteins - genetics
Cholesterol, HDL - blood
Cholesteryl ester transfer protein
Coronary artery disease
Coronary Artery Disease - genetics
Coronary heart disease
Follow-Up Studies
Genetic Predisposition to Disease - genetics
Genetics
Heart
Hepatic lipase
High density lipoprotein
Homozygote
Humans
Lipase - blood
Lipase - genetics
Male
Medical sciences
Middle Aged
Odds Ratio
Polymorphism, Single Nucleotide - genetics
Reverse cholesterol transport
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Summary:Abstract Cholesteryl ester transfer protein (CETP) and hepatic lipase (HL) are two HDL modifying proteins that have both pro- and anti-atherogenic properties. We hypothesized that CETP and HL synergistically affect HDL cholesterol and atherosclerotic risk. To test our hypothesis, we analysed the genotype frequencies of CETP Taq1B (rs708272) and LIPC -514C/T (rs1800588) polymorphisms in male coronary artery disease patients (CAD; n = 792) and non-symptomatic controls ( n = 539). Cases and controls had similar allele frequencies, but the occurrence of the combined genotypes differed ( p = 0.027). In CAD patients, 1.3% had the CETP- B2B2/ LIPC -TT genotype, with only 0.2% in controls ( p = 0.033). The presence of the CETP lowering B2 allele and the HL lowering LIPC -T allele synergistically increased HDL cholesterol from 0.87 ± 0.19 mmol/L in the B1B1/CC ( n = 183) to 1.21 ± 0.25 mmol/L in the B2B2/TT carriers ( n = 10). The B1B1/CC carriers had an increased CAD risk (OR 1.4; p = 0.025). Despite their high HDL cholesterol, the B2B2/TT individuals also had an increased CAD risk (OR 3.7; p = 0.033). In a 2-year follow up, the loss of coronary artery lumen diameter in these patients was higher than in all other patients combined (0.34 ± 0.70 versus 0.10 ± 0.29 mm; p = 0.044). We conclude that a high HDL cholesterol does not protect against coronary artery disease when associated with combined CETP- and HL-lowering gene variants.
ISSN:0021-9150
1879-1484
DOI:10.1016/j.atherosclerosis.2007.11.019