CETP TaqIB B2B2 genotype replicates its HDL cholesterol and coronary benefit in men with low HDL, VA-HIT trial finds (Arterioscler Thromb Vasc Biol 2002)

Original title: 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

Arterioscler Thromb Vasc Biol · 1 July 2002 · 7

Brousseau ME, O'Connor JJ, Ordovas JM, Collins D, Otvos JD, Massov T, McNamara JR, Rubins HB, Robins SJ, Schaefer EJ

Having previously reported in the Framingham Offspring Study (FOS) that the CETP TaqIB B2 allele is associated with higher HDL-cholesterol (HDL-C), decreased CETP activity, and reduced coronary heart disease (CHD) risk for B2B2 men, this study tested the relationship at the population level in 852 men from the Veterans Affairs HDL-C Intervention Trial (VA-HIT), which explored raising HDL in men with established CHD and low HDL-C. The B2B2 genotype was less frequent in VA-HIT (13.9%) than FOS (19.1%, -27%, P less than 0.03). As in FOS, VA-HIT B2B2 men had the highest mean HDL-C (32.6 mg/dL), followed by B1B2 (32.0 mg/dL) and B1B1 (30.9 mg/dL). B1B1 men, despite the least favorable baseline lipid profile, had the greatest triglyceride-lowering response to gemfibrozil (-34%, P=0.006). CETP TaqIB genotype was also associated with CHD end point risk, with an adjusted risk ratio of 0.52 for B2B2 men (P=0.08).

Original abstract

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 (< or =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.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.