Regulation of plasma HDL cholesterol and subfraction distribution by genetic and environmental factors. Associations between the TaqI B RFLP in the CETP gene and smoking and obesity.

Abstract

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 HDL 2 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 L ow plasma levels of high-density lipoprotein (HDL) are associated with increased coronary artery disease risk.1 -2 In addition, it has been found that clinical benefit is associated with a rise in HDL concentration in intervention trials. The Helsinki Heart Study 3 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, HDL 2 (1.063<d<1.125 g/mL) and HDL 3 (1.125<rf< 1.21 g/mL), and it is the former that is particularly associated with protection from coronary artery disease. 4 The strong inverse correlation between triglyceride concentration and HDL concentration 5 and HDL size in normal individuals 6 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 HDL 2 concentration. Multivariate analysis demonstrated that the Taql B polymorphism had an effect on HDL cholesterol and HDL 2 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 HDL 2 , 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 HDL 2 levels that is independent of plasma triglycerides and interacts with lifestyle factors. (Arterioscler Thromb. 1994;14:336-344.)Key Words • cholesteryl ester transfer...

TaqIB polymorphism in CETP gene: the influence on incidence of cardiovascular disease in statin-treated patients with familial hypercholesterolemia

“…Our finding that only 'never smokers' had a significant association of HDL-cholesterol levels with the B1 allele is in line with other studies. 4,5,16 Despite a more favorable baseline HDL-cholesterol, our patients with the B2B2 genotype had a higher event risk and a poor event-free survival, compared to carriers of the B1 allele. This finding is not in line with other studies that assessed cardiovascular event risks according to this polymorphism, and found that subjects with a B2 allele were more protected.…”

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy

“…Several previous studies have demonstrated such associations for HDL-C, specifically with SNP4 (TaqIB). [3][4][5]8,[35][36][37] In some reports, the association was seen only in subgroups, such as ex-and nonsmokers, 38 or in women, but not in men. 39 Alhough we could not replicate the association of an increased baseline HDL-C in the presence of the mutant B2 allele of SNP4, the strong stepwise decrease in CETP mass and activity associated with the number of B2 alleles of SNP4 clearly underlines such an expected effect on HDL-C. With respect to SNP 7 (A373P) and SNP8 (R451Q), the Copenhagen City Heart Study found a decrease in HDL-C and ApoA1 in carriers of the mutant allele, both in men and women.…”

Contribution of the cholesteryl ester transfer protein gene TaqIB polymorphism to the reduced plasma HDL-cholesterol levels found in abdominal obese men with the features of the insulin resistance syndrome

“…Thus, the difference between the B2B2 group and the B1B1 group was greater among subjects with a high alcohol intake. Furthermore, Freeman and colleagues 7 reported that B2B2 homozygotes had signi®cantly higher plasma HDL-chol concentrations than B1B1 homozygotes when subjects were relatively lean but this difference was attenuated when subjects in the upper tertile of BMI (26.2 ± 40.4 kgam 2 ) were compared. Taken together, these results reinforce the notion that environmental factors may exert more in¯uence on plasma HDL-chol concentrations in B2 than in B1 carriers.…”