TY - JOUR
T1 - An increased coronary risk is paradoxically associated with common cholesteryl ester transfer protein gene variations that relate to higher high-density lipoprotein cholesterol
T2 - A population-based study
AU - Borggreve, Susanna E.
AU - Hillege, Hans L.
AU - Wolffenbuttel, Bruce H. R.
AU - de Jong, Paul E.
AU - Zuurman, Mike W.
AU - van der Steege, Gerrit
AU - van Tol, Arie
AU - Dullaart, Robin P. F.
AU - PREVEND Study Group
PY - 2006/9
Y1 - 2006/9
N2 - Background: Several cholesteryl ester transfer protein (CETP) polymorphisms affect high-density lipoprotein (HDL) cholesterol, but the impact of CETP gene variants on incident coronary disease in the general population is uncertain after correction for their effect on HDL cholesterol.Design: We determined relationships between the CETP - 629C -> A promoter (n = 8141), the TaqIB (n = 8289), and the I405V (n = 8265) polymorphisms, serum lipids, C-reactive protein, and clinical factors with incident coronary heart disease (defined as death from or hospitalization for myocardial infarction, ischemic heart disease, or coronary intervention) during a median of 4.94 yr follow-up.Subjects: A predominantly Caucasian general population was studied.Results: HDL cholesterol was 0.08 mmol/liter higher in -629A carriers than in -629CC homozygotes (P <0.001). The unadjusted coronary hazard was 1.26 [ 95% confidence interval (CI), 0.95 - 1.68; P = 0.11] in A carriers compared with CC homozygotes and increased to 1.46 (95% CI, 1.10 - 1.95; P = 0.01) after adjustment for HDL cholesterol. This effect remained after additional adjustment for apolipoprotein A-I, triglycerides, C-reactive protein, age, and gender. Likewise, the HDL-cholesterol-adjusted hazard ratio was also higher in AA than in CC homozygotes (hazard ratio, 1.72; 95% CI, 1.22 - 2.42; P <0.01). Similar findings were obtained with the TaqIB polymorphism. The 405V allele was weakly associated with incident coronary heart disease after HDL cholesterol adjustment (P = 0.09).Conclusions: A common CETP promoter polymorphism, which beneficially contributes to higher HDL cholesterol, is paradoxically associated with increased incidence of coronary disease in the general population. Thus, CETP gene variation may affect coronary risk apart from the level of HDL cholesterol.
AB - Background: Several cholesteryl ester transfer protein (CETP) polymorphisms affect high-density lipoprotein (HDL) cholesterol, but the impact of CETP gene variants on incident coronary disease in the general population is uncertain after correction for their effect on HDL cholesterol.Design: We determined relationships between the CETP - 629C -> A promoter (n = 8141), the TaqIB (n = 8289), and the I405V (n = 8265) polymorphisms, serum lipids, C-reactive protein, and clinical factors with incident coronary heart disease (defined as death from or hospitalization for myocardial infarction, ischemic heart disease, or coronary intervention) during a median of 4.94 yr follow-up.Subjects: A predominantly Caucasian general population was studied.Results: HDL cholesterol was 0.08 mmol/liter higher in -629A carriers than in -629CC homozygotes (P <0.001). The unadjusted coronary hazard was 1.26 [ 95% confidence interval (CI), 0.95 - 1.68; P = 0.11] in A carriers compared with CC homozygotes and increased to 1.46 (95% CI, 1.10 - 1.95; P = 0.01) after adjustment for HDL cholesterol. This effect remained after additional adjustment for apolipoprotein A-I, triglycerides, C-reactive protein, age, and gender. Likewise, the HDL-cholesterol-adjusted hazard ratio was also higher in AA than in CC homozygotes (hazard ratio, 1.72; 95% CI, 1.22 - 2.42; P <0.01). Similar findings were obtained with the TaqIB polymorphism. The 405V allele was weakly associated with incident coronary heart disease after HDL cholesterol adjustment (P = 0.09).Conclusions: A common CETP promoter polymorphism, which beneficially contributes to higher HDL cholesterol, is paradoxically associated with increased incidence of coronary disease in the general population. Thus, CETP gene variation may affect coronary risk apart from the level of HDL cholesterol.
KW - URINARY ALBUMIN EXCRETION
KW - TYPE-2 DIABETES-MELLITUS
KW - LIPID TRANSFER PROTEINS
KW - INTIMA-MEDIA THICKNESS
KW - HEART-DISEASE
KW - TAQIB POLYMORPHISM
KW - CETP GENE
KW - ARTERY-DISEASE
KW - MYOCARDIAL-INFARCTION
KW - PROMOTER POLYMORPHISM
U2 - 10.1210/jc.2005-2322
DO - 10.1210/jc.2005-2322
M3 - Article
SN - 0021-972X
VL - 91
SP - 3382
EP - 3388
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -