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.

Additional Metadata
Keywords Atherosclerosis, Cholesteryl ester transfer protein, Coronary artery disease, Genetics, Hepatic lipase, High density lipoprotein, Reverse cholesterol transport
Persistent URL dx.doi.org/10.1016/j.atherosclerosis.2007.11.019, hdl.handle.net/1765/28961
Citation
van Acker, B.A.C, Botma, G.J, Zwinderman, A.H, Kuivenhoven, J.A, Dallinga-Thie, G.M, Sijbrands, E.J.G, … Verhoeven, A.J.M. (2008). High HDL cholesterol does not protect against coronary artery disease when associated with combined cholesteryl ester transfer protein and hepatic lipase gene variants. Atherosclerosis, 200(1), 161–167. doi:10.1016/j.atherosclerosis.2007.11.019