Genetics
CETP TaqIB B2 allele lowers CHD risk in men in the Framingham Offspring Study (Arterioscler Thromb Vasc Biol 2000)
Original title: Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study
In 1411 men and 1505 women from the Framingham Offspring Study, CETP TaqIB genotype (B2 allele frequency 0.444 in men, 0.433 in women) was significantly associated with decreased CETP activity. B1B1 individuals had lower HDL-cholesterol than B1B2 and B2B2 carriers in both men (1.07 vs 1.14 vs 1.18 mmol/L) and women (1.40 vs 1.46 vs 1.53 mmol/L, both P<0.001), and the B2 allele was associated with larger HDL and LDL particle size in men, and larger HDL particle size alone in women. The B2 allele's odds ratio for prevalent CHD was 0.696 (P=0.035) in men, attenuating to 0.735 (P=0.187) after adjusting for cardiovascular risk factors and HDL-C, indicating the protective effect was partly mediated through HDL-C; no protective effect was seen in women. CETP TaqIB genotype is thus a significant determinant of HDL-C, CETP activity, and lipoprotein size, translating into lower CHD risk in men specifically.
Original 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. Variations at the CETP locus have been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. 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 from 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 (HDL-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 index, systolic blood pressure, diabetes, smoking, alcohol consumption, beta-blocker 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 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.