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Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects: a study based on coronary angiography
1Internal Medicine 1, Nagoya City University Medical School, Nagoya, 467-8601, Aichi, Japan.
Insights
Cholesteryl ester transfer protein (CETP) mass in plasma does not directly correlate with coronary atherosclerosis. However, a specific CETP gene variant (B2B2 genotype) may offer protection against atherosclerosis by lowering CETP levels.
Area of Science:
- Cardiovascular Research
- Genetics
- Biochemistry
Background:
- Cholesteryl ester transfer protein (CETP) plays a role in lipid metabolism.
- The relationship between CETP mass, its gene polymorphisms, and coronary atherosclerosis requires further elucidation.
Purpose of the Study:
- To investigate the association between CETP mass, CETP gene polymorphisms (I405V and TaqIB), and coronary atherosclerosis in Japanese subjects.
- To determine the impact of CETP on lipid profiles and coronary artery disease.
Main Methods:
- Cross-sectional analysis of 110 Japanese patients undergoing coronary angiography.
- Measurements included CETP mass assay, genotyping for CETP polymorphisms, and analysis of plasma lipids and lipoproteins.
- Coronary angiography findings were assessed using coronary score (CS).
Main Results:
- CETP mass did not significantly correlate with coronary score or the presence of coronary heart disease (CHD).
- CETP mass correlated positively with total and LDL cholesterol but not HDL cholesterol.
- The TaqIB polymorphism (B2B2 genotype) was associated with lower CETP mass and potentially reduced atherosclerosis in patients with low CS.
Conclusions:
- Plasma CETP mass is not a direct determinant of coronary atherosclerosis in non-CETP-deficient individuals.
- The B2B2 genotype of CETP TaqIB polymorphism may confer a protective effect against atherosclerosis.
- CETP mass indirectly influences atherogenesis through its correlation with LDL cholesterol.
Abstract:
We undertook a cross-sectional analysis on CETP and atherosclerosis among Japanese subjects, by means of CETP mass assay, its gene polymorphism and coronary angiogram. The 110 consecutive patients who underwent coronary angiography were enrolled into the study except for those over 70 years and taking lipid-lowering drugs. Association was analyzed among plasma lipid and lipoproteins, CETP mass, its gene polymorphisms and the finding in coronary angiography. Four CETP-deficiency heterozygotes were identified and excluded from the analysis. CETP mass level showed neither significant correlation with the coronary score (CS) (r=0.06, P=0.52) nor the difference between the groups eventually diagnosed as coronary heart disease (CHD) positive and CHD negative (2.36+/-0.57 vs. 2.24+/-0.21, P=0.24). CETP mass correlated with the total and LDL cholesterol (r=0.43, P<0.001; r=0.36, P<0.001, respectively) but not with HDL cholesterol (r=0.08, P=0.40). While I405V polymorphism had no impact on CETP mass, HDL cholesterol or CS, CETP mass was low with TaqIB polymorphism (B1B1>B2B2, P<0.05) only in the low CS group (<4). Among the lipid and lipoprotein, HDL cholesterol had a greater impact than LDL cholesterol on coronary atherosclerosis. We concluded that CETP mass in plasma does not correlate with coronary atherosclerosis as whole in the non-CETP-deficient. However, the B2B2 genotype in CETP TaqIB polymorphism, only when it decreases the CETP level, may act as a protective factor against atherosclerosis. It should also be noted that CETP mass in general correlates to total and LDL cholesterol, so that it would be an indirect atherogenic parameter.