Regulation of Plasma HDL Cholesterol and Subfraction Distribution by Genetic and Environmental Factors Associations Between the Taql B RFLP in the CETP Gene and Smoking and Obesity

This study investigated in a healthy population (n=220) the association of the Taql B restriction fragment length polymorphism (RFLP) in the cholesteryl ester transfer protein (CETP) gene with plasma high-density lipoprotein (HDL) cholesterol concentration and subfraction distribution. A raised HDL cholesterol level was found in B2B2 homozygotes (B2 cutting site absent) and was associated specifically with a 45% increase in HDL2 compared with B1B1 homozygotes (B1B1, 77±39 mg/100 mL, mean±SD; B2B2, 112±59 mg/100 mL; /<0.01). Total plasma, very-low-density lipoprotein, and HDL triglyceride levels did not differ among the genotype groups, nor did plasma apolipoprotein AI levels {B1B1, 1.45+0.35 mg/mL, mean±SD; B2B2, 1.56±0.33 mg/ mL). Thus, the genetic variation appeared to be independent of metabolic factors that are known to regulate HDL levels. Plasma CETP exchange activity was unlikely to be the cause of Low plasma levels of high-density lipoprotein (HDL) are associated with increased coronary artery disease risk.In addition, it has been found that clinical benefit is associated with a rise in HDL concentration in intervention trials. The Helsinki Heart Study showed that a mean increase of 11% in HDL cholesterol levels was associated with a 34% reduction in coronary heart disease even after correction for other risk factors, including low-density lipoprotein (LDL) cholesterol and plasma triglyceride levels. Plasma HDL is composed of two main subfractions, HDL2 (1.063<d<1.125 g/mL) and HDL3 (1.125<rf< 1.21 g/mL), and it is the former that is particularly associated with protection from coronary artery disease. The strong inverse correlation between triglyceride concentration and HDL concentration and HDL size in normal individuals is thought to be due to triglyceride transfer from very-low-density lipoprotein (VLDL) and chylomicrons to HDL, with subsequent Received October 22, 1993; revision accepted November 16, 1993. From the Institute of Biochemistry, Royal Infirmary, and the Department of Statistics, University of Glasgow (A.P.H.), Glasgow, Scotland. Correspondence to Dilys Freeman, Department of Pathological Biochemistry, Royal Infirmary, Castle St, Glasgow, G4 OSF, Scotland, UK. the association, since it did not differ between genotype groups and was not correlated with HDL2 concentration. Multivariate analysis demonstrated that the Taql B polymorphism had an effect on HDL cholesterol and HDL2 that was independent of age, sex, body mass index, oral contraceptive use, exercise, alcohol consumption, and plasma triglycerides. In smokers, the presence of the B2B2 genotype did not result in increased HDL cholesterol or HDL2, whereas in obese subjects, the difference between B1B1 and B2B2 individuals was diminished. We conclude that the Taql B RFLP is associated with a quantitatively significant effect on plasma HDL2 levels that is independent of plasma triglycerides and interacts with lifestyle factors. (Arterioscler Thromb. 1994;14:336-344.)