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
Plasma triglyceride (TG) levels are inversely related to HDL-cholesterol levels and subjects with high TG and low HDL cholesterol have increased coronary heart disease (CHD) risk. Plasma cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to TG-rich lipoproteins. In this...
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| Format: | Article |
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Elsevier
1998-05-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520338761 |
| _version_ | 1818601215894749184 |
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| author | Can Bruce Dan S. Sharp Alan R. Tall |
| author_facet | Can Bruce Dan S. Sharp Alan R. Tall |
| author_sort | Can Bruce |
| collection | DOAJ |
| description | Plasma triglyceride (TG) levels are inversely related to HDL-cholesterol levels and subjects with high TG and low HDL cholesterol have increased coronary heart disease (CHD) risk. Plasma cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to TG-rich lipoproteins. In this study we determined the relationship between a common CETP amino acid polymorphism (I405V) and CETP and HDL levels and CHD prevalence in 576 men of Japanese ancestry in the Honolulu Heart Program cohort. This conservative substitution was associated with altered plasma CETP concentration (1.95 ± 0.54, 1.91 ± 0.57, and 1.77 ± 0.57 μg/ml for the II, IV and VV genotypes, respectively). The distribution of plasma CETP concentrations among the VV, but not II, men appeared bimodal (P < 0.01), suggesting the presence of a functionally significant CETP gene mutation(s) in a subset of V alleles. HDL-C levels were higher in VV than IV for II men (55.4 ± 17.4, 51.3 ± 16.6, 51.1 ± 17.0 mg/dl, P < 0.04). However, the increase in HDL was only significant in VV men with plasma TG > 165 mg/dl. Although CHD prevalence was not significantly different among the three genotypes in this population, in the subpopulation with high plasma TG, CHD prevalence appeared higher among VV than IV or II subjects (38% vs. 27% vs. 18%, P < 0.05 for an interaction of genotype and plasma TG levels). In fresh plasma from a separate group of normolipidemic subjects, the V/I polymorphism was not associated with any change in plasma CETP specific activity. The data suggest that a widespread and common CETP gene mutation(s) in linkage disequilibrium with 405V causes low CETP. Among hypertriglyceridemic men this is associated with higher HDL and possibly with increased CHD.—Bruce, C., 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. 1998. 39: 1071–1078. |
| first_indexed | 2024-12-16T12:47:51Z |
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| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T12:47:51Z |
| publishDate | 1998-05-01 |
| publisher | Elsevier |
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| spelling | doaj.art-c7b801b9c74b43c79ff23e26cb1e3a832022-12-21T22:31:14ZengElsevierJournal of Lipid Research0022-22751998-05-0139510711078Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemiaCan Bruce0Dan S. Sharp1Alan R. Tall2Division of Molecular Medicine, Columbia University, New York 10032Division of Epidemiology and Clinical Applications, Epidemiology and Biometry Program, National Heart, Lung and Blood Institutes, National Institutes of Health, Bethesda, MD 20892To whom correspondence should be addressed.; Division of Molecular Medicine, Columbia University, New York 10032Plasma triglyceride (TG) levels are inversely related to HDL-cholesterol levels and subjects with high TG and low HDL cholesterol have increased coronary heart disease (CHD) risk. Plasma cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from HDL to TG-rich lipoproteins. In this study we determined the relationship between a common CETP amino acid polymorphism (I405V) and CETP and HDL levels and CHD prevalence in 576 men of Japanese ancestry in the Honolulu Heart Program cohort. This conservative substitution was associated with altered plasma CETP concentration (1.95 ± 0.54, 1.91 ± 0.57, and 1.77 ± 0.57 μg/ml for the II, IV and VV genotypes, respectively). The distribution of plasma CETP concentrations among the VV, but not II, men appeared bimodal (P < 0.01), suggesting the presence of a functionally significant CETP gene mutation(s) in a subset of V alleles. HDL-C levels were higher in VV than IV for II men (55.4 ± 17.4, 51.3 ± 16.6, 51.1 ± 17.0 mg/dl, P < 0.04). However, the increase in HDL was only significant in VV men with plasma TG > 165 mg/dl. Although CHD prevalence was not significantly different among the three genotypes in this population, in the subpopulation with high plasma TG, CHD prevalence appeared higher among VV than IV or II subjects (38% vs. 27% vs. 18%, P < 0.05 for an interaction of genotype and plasma TG levels). In fresh plasma from a separate group of normolipidemic subjects, the V/I polymorphism was not associated with any change in plasma CETP specific activity. The data suggest that a widespread and common CETP gene mutation(s) in linkage disequilibrium with 405V causes low CETP. Among hypertriglyceridemic men this is associated with higher HDL and possibly with increased CHD.—Bruce, C., 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. 1998. 39: 1071–1078.http://www.sciencedirect.com/science/article/pii/S0022227520338761cholesteryl ester transfer proteinlipid transfer proteinhigh density lipoproteinshypertryiglyceridemiacoronary heart disease |
| spellingShingle | Can Bruce Dan S. Sharp Alan 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 Journal of Lipid Research cholesteryl ester transfer protein lipid transfer protein high density lipoproteins hypertryiglyceridemia coronary heart disease |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | cholesteryl ester transfer protein lipid transfer protein high density lipoproteins hypertryiglyceridemia coronary heart disease |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520338761 |
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