on June 6, 2002
Published online before print June 6, 2002, doi: 10.1161/01.ATV.0000024566.57589.2E
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Submitted on March 20, 2002
Accepted on May 15, 2002
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
Margaret E. Brousseau *;
From the Lipid Metabolism Laboratory (M.E.B., J.J.O., J.M.O., T.M., J.R.M., E.J.S.), JM-USDA-Human Nutrition Research Center on Aging at Tufts University and Department of Medicine, New England Medical Center, Boston, Mass; the Department of Veterans Affairs Cooperative Studies Program Coordinating Center (D.C.), West Haven, Conn; the Department of Biochemistry (J.D.O.), North Carolina State University, Raleigh; the Center for Chronic Disease Outcomes Research (H.B.R.), Veterans Affairs Medical Center, Minneapolis, Minn; and the Department of Medicine (S.J.R.), Boston University School of Medicine, Boston, Mass.
* To whom correspondence should be addressed. E-mail: mbrousseau{at}hnrc.tufts.edu.
Objective—We have previously reported that genetic variation at the cholesteryl ester transfer protein (CETP) TaqIB locus is correlated with plasma lipid levels and coronary heart disease (CHD) risk in the Framingham Offspring Study (FOS). In FOS, the B2 allele was associated with increased levels of high density lipoprotein (HDL) cholesterol (HDL-C), decreased CETP activity, and reduced CHD risk for men having the B2B2 genotype. The present study was undertaken to further define the relationship between this polymorphism and CHD risk at the population level.
Methods and Results—We tested for associations between the CETP TaqIB genotype and plasma lipoprotein levels, response to gemfibrozil therapy, and CHD end points in 852 men participating in the Veterans Affairs HDL-C Intervention Trial (VA-HIT), a study designed to explore the potential benefits of raising HDL levels in men having established CHD with low HDL-C (
40 mg/dL) as their primary lipid abnormality. In VA-HIT, 13.9% of the men had the B2B2 genotype relative to 19.1% of the men in FOS (-27%, P<0.03), whereas more men in VA-HIT had the B1B1 genotype (15%, P<0.05). Similar to our finding in FOS, B2B2 men in VA-HIT had the highest mean level of HDL-C (32.6±4.8 mg/dL), followed by B1B2 men (32.0±5.3 mg/dL), and, last, by B1B1 men (30.9±4.9 mg/dL). Interestingly, B1B1 men, who had the least favorable plasma lipid profile at baseline, had the greatest triglyceride-lowering response to gemfibrozil (-34%, P=0.006). CETP TaqIB genotype was also associated with the risk of CHD end points in VA-HIT, with an adjusted risk ratio of 0.52 for B2B2 men (P=0.08).
Conclusions—Our data demonstrate that in men with CHD and HDL deficiency, the CETP TaqI B2B2 genotype is (1) significantly reduced and (2) associated with higher levels of plasma HDL-C and lower CHD risk. Together with our earlier report, these results support the concept that increased HDL-C levels, resulting from reduced CETP activity, are associated with decreased CHD risk.
Key words: cholesteryl ester transfer protein • coronary heart disease • high density lipoproteins • polymorphism • Veterans Affairs HDL-C Intervention Trial
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