Influence of polymorphism (RFLP-sstI) at the apolipoprotein C-III gene locus on the lipoprotein metabolism and insulin resistance in essential hypertensive patients. Interaction between gender and genetic polymorphism

Abstract

With respect to the general population, hypertensive patients show an increase in plasma total cholesterol and triglycerides, a decrease in HDL-cholesterol (HDLc) and a higher degree of insulin resistance. Apolipoprotein C-III (apo C-III) plays a regulatory role in the catabolism of triacylglycerol-rich lipoproteins. The S2 allele has been associated with elevated plasma triglycerides concentration, blood pressure and increased risk of myocardial infarction, all of which are characteristic of an insulin resistant state. The aim of this study was to investigate the SstI polymorphism of the apo C-III gene locus on the lipoprotein metabolism, apolipoproteins and basal glucose and insulin levels in essential hypertensive patients. We also examined the influence of the S1S2 allele on blood pressure and the interaction of the mutation at the apo C-III gene and the gender. We studied 104 essential hypertensive patients (59 males and 45 females) determining the carriers of the S2 allele of the genetic polymorphism in the apo C-III gene by polymerase chain reaction, lipoprotein metabolism by standard laboratory methods and ultracentrifugation, apolipoproteins A-I and B by immunoturbidimetry and basal glucose and insulin levels by enzymatic method and radioimmunoassay, respectively. The frequency for the carriers of the SstI minor allele S2 (S1S2 genotype) was 0.17. Patients with the rare S2 allele compared with those with S1S1 allele showed higher plasma triglycerides, total cholesterol and apo B (255.9 +/- 114.6 vs 135.8 +/- 89.1; 250.6 +/- 56.6 vs 214.8 +/- 47.9 and 128.7 +/- 34.8 vs 103.1 +/- 28.6 respectively). Furthermore, basal glucose, insulin levels in S2 allele, and the rate Tg-VLDL/HDLc were increased in the same group. Subgroup analysis revealed that the association between these polymorphism and lipoprotein metabolism, apolipoprotein and basal glucose and insulin levels occurred predominantly in females. A study on the effect of the interaction between this mutation with gender revealed an additive effect on changes in total triglycerides levels. However age, blood pressure and body mass index were similar in both groups of patients (S1S1 and S1S2 genotypes). These results provide evidence of interaction between gender and the Sst1 polymorphism of the apo C-III on lipoprotein metabolism and insulin resistance in essential hypertensive patients. However, the studied mutation does not contribute to blood pressure levels in essential hypertensive patients (crossover study).