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

Abstract

OBJECTIVE: The aim of this study was to examine the relation between the CETP-TaqIB polymorphism and reduced plasma HDL-cholesterol levels commonly observed among men characterized by abdominal obesity and features of the insulin resistance syndrome. SUBJECTS: A total of 187 sedentary men, non-smokers and free from metabolic disorders were classi®ed on the basis of their CETP-TaqIB genotype. RESULTS: Plasma HDL and HDL 3 -cholesterol concentrations as well as the CETP activity were signi®cantly different between the three genotypes, B1B1 men having signi®cantly lower HDL and HDL 3 -cholesterol levels and higher CETP activity than B2B2 homozygotes. A 2Â3 ANOVA was used to determine the source of variation of plasma HDL and HDL 2 -cholesterol levels among the three genotypic groups of men divided on the basis of either a high ( ! 27 kgam 2 ) or a low (`27 kgam 2 ) BMI, a high ( ! 130 cm 2 ) or a low (`130 cm 2 ) accumulation of visceral adipose tissue assessed by computed tomography, or a low versus a high fasting plasma insulin concentration (using the median value as a cutoff point). The effect of the CETP genotype observed on plasma HDL-cholesterol concentrations was attenuated among men with features of the insulin resistance syndrome. It seems that the expected raising effect of the B2 allele on plasma HDL-cholesterol concentrations was blunted in the presence of a BMI ! 27 kgam 2 , a high accumulation of visceral adipose tissue or hyperinsulinaemia. CONCLUSION: Our data indicate that the CETP gene TaqIB polymorphism in¯uences plasma CETP activity on one hand and plasma HDL-cholesterol concentrations on the other hand among men. The association between the TaqIB polymorphism and plasma HDL-cholesterol concentrations is altered by the presence of abdominal obesity and some features of the insulin resistance syndrome.

Cholesteryl Ester Transfer Protein TaqIB Variant, High-Density Lipoprotein Cholesterol Levels, Cardiovascular Risk, and Efficacy of Pravastatin Treatment

“…In addition to smoking and male sex, obesity, visceral fat accumulation, and hyperinsulinemia have also been reported to blunt the effect of TaqIB genotype on HDL-C levels. 13,14 In the present analysis, we were only able to study an interaction with BMI, which we did not detect. Given the fact that the interactions described in the literature were of greater magnitude than the detectable effect size shown in Table 4, we conclude that an interaction between TaqIB genotype and BMI is unlikely.…”

“…We investigated whether our pooled dataset provided any evidence for the published interactions between TaqIB genotype and sex, 11,12 smoking, 8,13 BMI, 13,14 and use of alcohol. 15 The present meta-analysis provides some evidence that interactions exist for both sex and smoking (Pϭ0.02 for each), such that the effect of TaqIB genotype on HDL-C levels was attenuated among men and among smokers.…”

“…8,9 Such inconsistencies are often encountered among genetic association studies and can be due factors such as genetic admixture or lack of statistical power. 10 In this specific case, an alternative explanation may derive from proposed interactions with sex, 11,12 smoking, 8,13 body mass index (BMI), 13,14 and use of alcohol, 15 all modifiers of CETP action, HDL-C levels, and CAD risk. In view of our recent report about an interaction between CETP plasma levels and triglyceride levels, 16 we also explored a potential interaction between TaqIB genotype and triglyceride levels.…”

Genetic epistasis in the VLDL catabolic pathway is associated with deleterious variations on triglyceridemia in obese subjects

“…This is concordant with our earlier studies. [37][38][39][40] Our results specifically illustrate that combinations of genetic factors sequentially involved in the VLDL catabolic pathway might influence the expression of the 'hypertriglyceridemic-waist' phenotype. Prevention of the risk associated with the 'hypertriglyceridemic-waist' phenotype importantly relies on intervention on life habits (diet, physical activity, etc.)…”

Association of the CETP TaqIB Polymorphism with Coronary Artery Disease in Type 2 Diabetic Patients

“…Some studies have reported no relationship between the TaqIB polymorphism and HDL-C levels in T2DM patients (29,30) while Kawasaki observed conversely. Several factors are involved in this relationship including gender, smoking and body mass index (BMI) (31,32). Considering the key role of CETP in the metabolism of lipoproteins, different polymorphisms in the CETP gene may affect blood lipid parameters.…”