High HDL cholesterol does not protect against coronary artery disease when associated with combined cholesteryl ester transfer protein and hepatic lipase gene variants.
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.
van Acker
Bernadette A C
BA
Department of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands.
Botma
Gert-Jan
GJ
Zwinderman
Aeilko H
AH
Kuivenhoven
Jan Albert
JA
Dallinga-Thie
Geesje M
GM
Sijbrands
Eric J G
EJ
Boer
Jolanda M A
JM
Seidell
Jacob C
JC
Jukema
J Wouter
JW
Kastelein
John J P
JJ
Jansen
Hans
H
Verhoeven
Adrie J M
AJ
D000368:Aged; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000235:genetics*; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008049:Lipase / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; C504173:LIPC protein, human; D008049:Lipase