The C766T low-density lipoprotein receptor related protein polymorphism and coronary artery disease, plasma lipoproteins, and longevity in the Czech population

Abstract

Low-density lipoprotein receptor related protein (LRP) is a multifunctional endocytic receptor involved in various biological processes including the regulation of the coagulation-fibrinolysis balance, the lipoprotein metabolism, and cellular migration, all of which relate to the development of atherosclerosis. Polymorphisms affecting the function or expression of LRP may thus influence the individual risk of atherosclerosis development. This study investigated the association between the C766T LRP polymorphism, coronary artery disease (CAD), and plasma lipoprotein levels in a large sample of Caucasian subjects of Czech nationality. In addition, the 4G/5G promoter polymorphism of the gene coding for plasminogen activator inhibitor 1 (PAI-1), the known ligand of LRP with strong antifibrinolytic potential, was ascertained to investigate its possible association with CAD. Both polymorphisms were studied using polymerase chain reaction analysis in 654 patients with angiographically confirmed CAD and in 525 controls. No statistically significant differences in allele frequencies of the polymorphisms studied were detected between patients and controls, even when men, women, hypertonic, and type II diabetic subjects were compared separately. However, the frequency of the T allele of the LRP polymorphism was significantly higher in patients than controls when only subjects with the 5G/5G PAI-1 genotype were analyzed. In addition, the T LRP allele frequency was significantly lower in subjects aged 60 years or over than in those who were younger in both groups. No significant association was observed between the LRP or PAI-1 polymorphisms and plasma lipoprotein levels in the CAD patients. Our results demonstrate that the T allele of the C766T LRP polymorphism is negatively related to longevity, and that it increases the risk of CAD development in subjects with the 5G/5G PAI-1 genotype.