Submitted to: Arteriosclerosis Thrombosis and Vascular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/29/1999
Publication Date: 5/1/2000
Citation: ORDOVAS, J.M., CUPPLES, A.L., CORELLA, D., OTVOS, J.D., OSGOOD, D., MARTINEZ, A., LAHOZ, C., COLTELL, O., WILSON, P.W., SCHAEFER, E.J. ASSOCIATION OF THE CETP TAQIB POLYMORPHISM WITH VARIATIONS IN LIPOPROTEIN SUBCLASSES AND CORONARY HEART DISEASE: THE FRAMINGHAM OFFSPRING STUDY. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY. 2000;20(5):1323-9. Interpretive Summary: Lipoproteins are particles carrying cholesterol and fats in the bloodstream. Cholesteryl ester transfer protein is a protein that transport lipids (cholesterol and triglycerides) between lipoproteins. This protein may play a key role in reverse cholesterol transport, the mechanism by which excess cholesterol from the cells is removed from the body. In this paper we show that a frequent mutation in the cholesteryl ester transfer protein gene is associated with significant variations in the lipoprotein profile in men and women. Moreover, male subjects that have this mutation have a much lower risk of developing coronary artery disease than those subjects that do not have such mutation. This finding can be used to differentiate among individuals according to their cardiovascular risk and to target those subjects at higher risk for more aggressive dietary therapy.
Technical Abstract: Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles, a key step in reverse cholesterol transport in humans. The associations of the common CETP polymorphism, TaqIB in intron 1, with lipoprotein levels and particle size distribution, CETP activity and coronary heart disease (CHD) risk were examined in a population based sample of 1411 men and 1505 women Framingham Offspring Study participants. The B2 allele frequency was 0.444 in men and 0.433 in women, and its presence was significantly (p<0.05) associated with decreased CETP activity. B1B1 men had lower HDL-C levels (1.07 mmol/L) as compared with B1B2 (1.14 mmol/L) and B2B2 subjects (1.18 mmol/L) (p <0.001). Likewise, B1B1 women had lower HDL-C levels (1.40 mmol/L) as compared with B1B2 (1.46 mmol/L) and B2B2 subjects (1.53 mmol/L) (p <0.001). In men the B2 allele was associated with increased particle size for both HDL and low-density lipoproteins (LDL). In women, a similar effect was demonstrated only for HDL particle size. The odds ratio (OR) for prevalent CHD associated with the B2 allele was 0.696 (p=0.035) in men. After adjusting for age, body mass index, systolic blood pressure, diabetes, smoking, alcohol consumption, beta-blocker use, total cholesterol and HDL-C, this OR was 0.735 (p = 0.187), suggesting that the protective effect of the B2 allele was due in part to its association with HDL-C levels. No significant protective effects were observed in women. These data demonstrate that variation at the CETP gene locus is a significant determinant of HDL-C levels, CETP activity and lipoprotein size in this population. Moreover, these effects appear to translate into a lower CHD risk among those men with the B2 allele.