Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:560-568
© 1997 American Heart Association, Inc.
Articles |
Heterogeneity at the CETP Gene Locus
Influence on Plasma CETP Concentrations and HDL Cholesterol Levels
From the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (J.A.K., H.A.S., G.-J.B., J.J.P.K.); Department of Human Genetics, Sylvius Laboratory, Leiden University (P.de K.); and Department of Chronic Diseases and Environmental Epidemiology, National Institute of Public Health and Environmental Protection, Bilthoven (J.M.A.B, J.C.S.), The Netherlands; and the Atherosclerosis Specialty Laboratory, Department of Pathology and Laboratory Medicine, St Paul's Hospital and University of British Columbia, Canada (P.H.P.).
Correspondence to J.A. Kuivenhoven, Academic Medical Center, Department of Vascular Medicine (G1-114), Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail kuif{at}wnet.bos.nl.
Abstract This study was designed to investigate the association(s) between heterogeneity at the cholesteryl ester transfer protein (CETP) gene locus, CETP plasma concentrations, and HDL cholesterol levels. Healthy men with the lowest, median, and highest deciles of HDL cholesterol were selected from a large population database. We accounted for factors that are known to influence HDL cholesterol levels, such as smoking, exercise, body mass index, alcohol consumption, and blood pressure. Plasma CETP concentrations were measured, and we determined the allele frequency distribution of six CETP DNA polymorphisms. The group with low HDL cholesterol exhibited a significant increase in CETP concentration compared with both the median and high HDL cholesterol groups, whereas CETP concentrations did not differ among the groups with median and high HDL cholesterol. The allele frequency distributions of the TaqIB (intron 1), Msp I (intron 8), and Rsa I (exon 14) polymorphisms differed significantly between the groups with low and high HDL cholesterol. Further analysis revealed that the Msp I polymorphism had a 1.5-fold larger impact on CETP concentration than the TaqIB polymorphism and a fivefold larger impact than the Rsa I polymorphism. In conclusion, we demonstrated that heterogeneity at the CETP gene locus is correlated with CETP plasma concentrations and HDL cholesterol levels. More specifically, our data indicate the presence of a strong association between common variants of the CETP gene, high plasma CETP concentrations, and consequently hypoalphalipoproteinemia in healthy white men.
Key Words: restriction fragment length polymorphism • cholesteryl ester transfer protein • high-density lipoprotein • coronary artery disease • haplotyping
This article has been cited by other articles:
 |
|
 |
|
  A. Thompson, E. Di Angelantonio, N. Sarwar, S. Erqou, D. Saleheen, R. P. F. Dullaart, B. Keavney, Z. Ye, and J. Danesh Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk JAMA, June 18, 2008; 299(23): 2777 - 2788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Spielmann, A. S. Leon, D. C. Rao, T. Rice, J. S. Skinner, C. Bouchard, and T. Rankinen CETP genotypes and HDL-cholesterol phenotypes in the HERITAGE Family Study Physiol Genomics, September 11, 2007; 31(1): 25 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Horne, N. J. Camp, J. L. Anderson, C. P. Mower, J. L. Clarke, M. J. Kolek, J. F. Carlquist, and for the Intermountain Heart Collaborative Study Gr Multiple Less Common Genetic Variants Explain the Association of the Cholesteryl Ester Transfer Protein Gene With Coronary Artery Disease J. Am. Coll. Cardiol., May 22, 2007; 49(20): 2053 - 2060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Borggreve, H. L. Hillege, B. H. R. Wolffenbuttel, P. E. de Jong, S. J. L. Bakker, G. van der Steege, A. van Tol, R. P. F. Dullaart, and on behalf of the PREVEND Study Group The Effect of Cholesteryl Ester Transfer Protein -629C->A Promoter Polymorphism on High-Density Lipoprotein Cholesterol Is Dependent on Serum Triglycerides J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4198 - 4204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. S. E. Albert, P. N. Duchateau, S. S. Deeb, C. R. Pullinger, M. H. Cho, D. C. Heilbron, M. J. Malloy, J. P. Kane, and B. G. Brown Apolipoprotein L-I is positively associated with hyperglycemia and plasma triglycerides in CAD patients with low HDL J. Lipid Res., March 1, 2005; 46(3): 469 - 474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. de Grooth, A. H. E. M. Klerkx, E. S. G. Stroes, A. F. H. Stalenhoef, J. J. P. Kastelein, and J. A. Kuivenhoven A review of CETP and its relation to atherosclerosis J. Lipid Res., November 1, 2004; 45(11): 1967 - 1974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Keavney, A. Palmer, S. Parish, S. Clark, L. Youngman, J. Danesh, C. McKenzie, M. Delepine, M. Lathrop, R. Peto, et al. Lipid-related genes and myocardial infarction in 4685 cases and 3460 controls: discrepancies between genotype, blood lipid concentrations, and coronary disease risk Int. J. Epidemiol., October 1, 2004; 33(5): 1002 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A Pereira, R. M Weggemans, D. R Jacobs Jr, P. J Hannan, P. L Zock, J. M Ordovas, and M. B Katan Within-person variation in serum lipids: implications for clinical trials Int. J. Epidemiol., June 1, 2004; 33(3): 534 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Morabia, E. Cayanis, M. C. Costanza, B. M. Ross, M. S. Flaherty, G. B. Alvin, K. Das, and T. C. Gilliam Association of extreme blood lipid profile phenotypic variation with 11 reverse cholesterol transport genes and 10 non-genetic cardiovascular disease risk factors Hum. Mol. Genet., November 1, 2003; 12(21): 2733 - 2743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Barzilai, G. Atzmon, C. Schechter, E. J. Schaefer, A. L. Cupples, R. Lipton, S. Cheng, and A. R. Shuldiner Unique Lipoprotein Phenotype and Genotype Associated With Exceptional Longevity JAMA, October 15, 2003; 290(15): 2030 - 2040. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Boekholdt and J. F. Thompson Natural genetic variation as a tool in understanding the role of CETP in lipid levels and disease J. Lipid Res., July 1, 2003; 44(6): 1080 - 1093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Anderson and J. F. Carlquist Genetic polymorphisms of hepatic lipase and cholesteryl ester transfer protein, intermediate phenotypes, and coronary risk: Do they add up yet? J. Am. Coll. Cardiol., June 4, 2003; 41(11): 1990 - 1993. [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Lottenberg, V. S. Nunes, E. R. Nakandakare, M. Neves, M. Bernik, L. Lagrost, J. E. dos Santos, and E. Quintao The Human Cholesteryl Ester Transfer Protein I405V Polymorphism Is Associated with Plasma Cholesterol Concentration and Its Reduction by Dietary Phytosterol Esters J. Nutr., June 1, 2003; 133(6): 1800 - 1805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Parolini, G. Chiesa, Y. Zhu, T. Forte, S. Caligari, E. Gianazza, M. G. Sacco, C. R. Sirtori, and E. M. Rubin Targeted Replacement of Mouse Apolipoprotein A-I with Human ApoA-I or the Mutant ApoA-IMilano. EVIDENCE OF APOA-IM IMPAIRED HEPATIC SECRETION J. Biol. Chem., February 7, 2003; 278(7): 4740 - 4746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H.E.M. Klerkx, M. W.T. Tanck, J. J.P. Kastelein, H. O.F. Molhuizen, J. W. Jukema, A. H. Zwinderman, and J. A. Kuivenhoven Haplotype analysis of the CETP gene: not TaqIB, but the closely linked -629C->A polymorphism and a novel promoter variant are independently associated with CETP concentration Hum. Mol. Genet., January 15, 2003; 12(2): 111 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bansal, D. van den Boom, S. Kammerer, C. Honisch, G. Adam, C. R. Cantor, P. Kleyn, and A. Braun Association testing by DNA pooling: An effective initial screen PNAS, December 24, 2002; 99(26): 16871 - 16874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-a. Wu, M. Tsujita, K. Okumura-Noji, S. Usui, H. Kakuuchi, M. Okazaki, and S. Yokoyama Cholesteryl Ester Transfer Protein Expressed in Lecithin Cholesterol Acyltransferase-Deficient Mice Arterioscler Thromb Vasc Biol, August 1, 2002; 22(8): 1347 - 1353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Brousseau, J. J. O'Connor Jr, J. M. Ordovas, D. Collins, J. D. Otvos, T. Massov, J. R. McNamara, H. B. Rubins, S. J. Robins, and E. J. Schaefer Cholesteryl Ester Transfer Protein TaqI B2B2 Genotype Is Associated With Higher HDL Cholesterol Levels and Lower Risk of Coronary Heart Disease End Points in Men With HDL Deficiency: Veterans Affairs HDL Cholesterol Intervention Trial Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1148 - 1154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Kawasaki, H. Tahara, M. Emoto, T. Shoji, and Y. Nishizawa Relationship Between TaqIB Cholesteryl Ester Transfer Protein Gene Polymorphism and Macrovascular Complications in Japanese Patients With Type 2 Diabetes Diabetes, March 1, 2002; 51(3): 871 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Miltiadous, M. A. Cariolou, and M. Elisaf HDL Cholesterol Levels in Patients with Molecularly Defined Familial Hypercholesterolemia Ann. Clin. Lab. Sci., January 1, 2002; 32(1): 50 - 54. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Teupser, W. Rupprecht, P. Lohse, and J. Thiery Fluorescence-based Detection of the CETP TaqIB Polymorphism: False Positives with the TaqMan-based Exonuclease Assay Attributable to a Previously Unknown Gene Variant Clin. Chem., May 1, 2001; 47(5): 852 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hadjadj, Y. Gallois, G. Simard, B. Bouhanick, P. Passa, A. Grimaldi, P. Drouin, J. Tichet, and M. Marre Lack of relationship in long-term type 1 diabetic patients between diabetic nephropathy and polymorphisms in apolipoprotein {varepsilon}, lipoprotein lipase and cholesteryl ester transfer protein Nephrol. Dial. Transplant., December 1, 2000; 15(12): 1971 - 1976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. W. Rittershaus, D. P. Miller, L. J. Thomas, M. D. Picard, C. M. Honan, C. D. Emmett, C. L. Pettey, H. Adari, R. A. Hammond, D. T. Beattie, et al. Vaccine-Induced Antibodies Inhibit CETP Activity In Vivo and Reduce Aortic Lesions in a Rabbit Model of Atherosclerosis Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2106 - 2112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. M. Diekman, N. Anghelescu, E. Endert, O. Bakker, and W. M. Wiersinga Changes in Plasma Low-Density Lipoprotein (LDL)- and High-Density Lipoprotein Cholesterol in Hypo- and Hyperthyroid Patients Are Related to Changes in Free Thyroxine, Not to Polymorphisms in LDL Receptor or Cholesterol Ester Transfer Protein Genes J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1857 - 1862. [Abstract] [Full Text]
|
|
|
|
|
|
J. M. Ordovas, L. A. Cupples, D. Corella, J. D. Otvos, D. Osgood, A. Martinez, C. Lahoz, O. Coltell, P. W. F. Wilson, and E. J. Schaefer Association of Cholesteryl Ester Transfer Protein-TaqIB Polymorphism With Variations in Lipoprotein Subclasses and Coronary Heart Disease Risk : The Framingham Study Arterioscler Thromb Vasc Biol, May 1, 2000; 20(5): 1323 - 1329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Agerholm-Larsen, B. G. Nordestgaard, R. Steffensen, G. Jensen, and A. Tybjarg-Hansen Elevated HDL Cholesterol Is a Risk Factor for Ischemic Heart Disease in White Women When Caused by a Common Mutation in the Cholesteryl Ester Transfer Protein Gene Circulation, April 25, 2000; 101(16): 1907 - 1912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dachet, O. Poirier, F. Cambien, J. Chapman, and M. Rouis New Functional Promoter Polymorphism, CETP/-629, in Cholesteryl Ester Transfer Protein (CETP) Gene Related to CETP Mass and High Density Lipoprotein Cholesterol Levels : Role of Sp1/Sp3 in Transcriptional Regulation Arterioscler Thromb Vasc Biol, February 1, 2000; 20(2): 507 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Riemens, A. Van Tol, B. K. Stulp, and R. P. F. Dullaart Influence of insulin sensitivity and the TaqIB cholesteryl ester transfer protein gene polymorphism on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities and their response to hyperinsulinemia in non-diabetic men J. Lipid Res., August 1, 1999; 40(8): 1467 - 1474. [Abstract] [Full Text]
|
|
|
|
|
|
C. Bruce, D. S. Sharp, and A. R. Tall Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia J. Lipid Res., May 1, 1998; 39(5): 1071 - 1078. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. A. Kuivenhoven, J. W. Jukema, A. H. Zwinderman, P. de Knijff, R. McPherson, A. V.G. Bruschke, K. I. Lie, J. J.P. Kastelein, and The Regression Growth Evaluation Statin Study Grou The Role of a Common Variant of the Cholesteryl Ester Transfer Protein Gene in the Progression of Coronary Atherosclerosis N. Engl. J. Med., January 8, 1998; 338(2): 86 - 93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Rosenthal and R. S. Schwartz In Search of Perverse Polymorphisms N. Engl. J. Med., January 8, 1998; 338(2): 122 - 124. [Full Text]
|
|