Association of cholesteryl eater transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk - The Framingham study

Cholesteryl ester transfer protein (CETP) facilitates the exchange of trigl ycerides and cholesteryl esters between lipoprotein particles, a key step i n reverse cholesterol transport in humans. Variations at the CETP locus hav e been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. The associations of the co mmon CETP polymorphism, TaqIB in intron 1, with lipoprotein levels and part icle size distribution, CETP activity, and coronary heart disease (CHD) ris k were examined in a population-based sample of 1411 men and 1505 women fro m the Framingham Offspring Study. 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 cholesterol (I-IDL-C) levels (1.07 mmol/L) compared with B1B2 (1.14 mmol/L) and B2B2 (1.18 mmol/L ) men (P<0.001). Likewise, B1B1 women had lower HDL-C levels (1.40 mmol/L) compared with B1B2 (1.46 mmol/L) and B2B2 (1.53 mmol/L) women (P<0.001). In men, the B2 allele was associated with increased particle size for HDL and low density lipoprotein. In women, a similar effect was demonstrated only for HDL particle size. The odds ratio for prevalent CHD associated with the B2 allele was 0.696 (P=0.035) in men, After adjusting for age, body mass i ndex, systolic blood pressure, diabetes, smoking, alcohol consumption, P-bl ocker use, total cholesterol, and HDL-C, this odds ratio was 0.735 (P=0.187 ), suggesting that the protective effect of the B2 allele was due in part t o 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 lipo protein size in this population. Moreover, these effects appear Co translat e into a lower CHD risk among those men with the BZ allele.