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

BAC Acker, GJ (Gerrit Jan) Botma, AH Zwinderman, JA Kuivenhoven, GM Dallinga-Thie, E.J.G. Sijbrands, JMA Boer, JC Seidell, JW Jukema, JJP Kastelein, H Jansen, Adrie Verhoeven

Research output: Contribution to journalArticleAcademicpeer-review

53 Citations (Scopus)

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 Taq 1B (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. (C) 2007 Elsevier Ireland Ltd. All rights reserved.
Original languageUndefined/Unknown
Pages (from-to)161-167
Number of pages7
JournalAtherosclerosis
Volume200
Issue number1
DOIs
Publication statusPublished - 2008

Cite this