Cholesteryl ester transfer protein TaqIB polymorphism and its relation to parameters of the insulin resistance syndrome in an Austrian cohort.

The cholesteryl ester transfer protein (CETP) is responsible for the exchange of triglycerides and cholesteryl esters between lipoprotein particles leading to an increased hepatic clearance of HDL-cholesteryl esters. A high CETP activity reduces serum HDL levels, whereas persons without CETP activity have high HDL levels. We investigated the association of the TaqIB CETP polymorphism and various parameters of the insulin resistance syndrome in a cross sectional population based study. We included 1029 persons without known cardiovascular disease or diabetes mellitus consecutively enrolled in our SAPHIR program (Salzburg Atherosclerosis Prevention program in persons with a High Infarction Risk). Numerous clinical and laboratory data were accomplished. Insulin sensitivity was measured by a short insulin tolerance test. The TaqIB CETP polymorphism was determined by PCR, TaqI restriction and electrophoresis. 35.2% were homozygous for the prevalence (B1B1), 46.7% were heterozygous (B1B2), and 18.1% homozygous for the absence (B2B2) of the restriction site. HDL cholesterol and apolipoprotein A1 were lower and small dense low-density lipoproteins (sdLDL) higher in B1B1 compared to B2B1 and B2B2 persons. In women, we found a significant interaction effect between CETP genotype and adiposity for HDL cholesterol. B1B1 women with a BMI and a waist circumference above the median had 9.7 mg/dl lower HDL than B1B2 and 9.1 mg/dl lower HDL than B2B2 women (P < 0.001). In men, no interaction effect but a marked genotype to HDL correlation was found. There was a high CETP effect on sdLDL detected in men (P = 0.001). B1B1 men had sdLDL in 36%, B1B2 in 24.6%, and B2B2 in only 14.5%. Men with adiposity and insulin resistance had twice as many sdLDL as insulin sensitive men. We found a significant sex specific effect of the TaqIB CETP polymorphism on the insulin resistance parameters HDL-cholesterol and sdLDL in an Austrian population based study.

Intima media thickness of carotid arteries is reduced in heterozygous carriers of the Gly972Arg variant in the insulin receptor substrate-1 gene.

BACKGROUND: The Gly972Arg mutation in the IRS-1 gene has been found to be associated with insulin resistance and type II diabetes. A recently published study described an association between the Arg allele and an increased risk for coronary artery disease. In the present study we asked whether the presence of the codon 972 mutation in the IRS-1 gene is associated with higher IMT values of the carotid arteries. MATERIALS AND METHODS: To address this question, genotypes of the codon 972 polymorphism were determined in 1018 healthy unrelated individuals aged 40-65 years. Three homozygous carriers of the mutation were excluded for statistical analysis. In all subjects, intima media thickness (IMT) and B-scores of carotid arteries as well as a large number of metabolic parameters were determined. RESULTS: Heterozygous carriers of the Arg972 allele exhibited significantly lower IMT and B-score values than noncarriers. Total cholesterol, LDL-cholesterol and serum levels of apolipoprotein B were significantly lower in the carriers. Furthermore, a significant interaction between Gly972Arg-carrier status and mean daytime 24-h systolic blood pressure with regard to IMT could be observed; carriers with a systolic blood pressure above the median had lower IMT values than carriers with a systolic blood pressure equal or below the median. All these effects were more pronounced in females and remained significant after adjustment for sex, age, BMI, systolic blood pressure and serum apolipoprotein B levels. No significant differences between the carriers and the noncarriers could be found for BMI, insulin sensitivity or frequency of type II diabetes. CONCLUSIONS: The results of our study demonstrate that the presence of the Arg972 allele is associated with lower IMT values of the carotid arteries. This finding is partly explained by lower serum levels of apolipoprotein B in carriers. The protective effect of the Gly972 Arg mutation seems to be stronger in the presence of a higher systolic blood pressure. Our data contradict previous findings suggesting an increased risk for insulin resistance, type II diabetes and atherosclerotic vascular disease in carriers of the mutation.