Role of the apoa5 gene in lipid and fat-soluble vitamin metabolism

Identificador:  TDX:635

Handle: https://hdl.handle.net/20.500.11797/TDX635

Autors:  Guardiola Guionnet, Montserrat

Resum:
Cardiovascular disease is the main cause of mortality in industrialised countries. Its high prevalence is mainly due to environmental factors (sedentary lifestyle, saturated fat rich diet and tobacco consumption, among others), which together with genetic predisposition could result in increased disease risk. One of the key factors in the development of atherosclerosis are circulating lipids which are guided by the apolipoproteins (APO). The malfunctioning of these proteins due to genetic variants could affect, for example, the concentration and circulating time of lipids. The APOA5 is a key gene modulating triglyceride (TG) metabolism, and our hypothesis is that APOA5 may also modify the circulating levels of other metabolic components highly linked to TG by influencing the synthesis and secretion of TG-rich particles.Using the genetic variability of the APOA5 gene in two populations, healthy men and type 2 diabetic patients, we have described that carriers of the -1131T>C variant present with more than 15% higher TG levels, being this effect mainly due to a greater TG content in circulating VLDL particles. We have also described that this variant affects vitamin E concentrations in both populations, increasing its levels in circulation. Vitamin E is a potent antioxidant, but this variant does not affect the oxidative status of the subjects, because its levels rise in the same proportion than TG do.Since the circulating TG levels can be affected by other factors such as the pharmacological treatment (for example, the protease inhibitors used for the AIDS therapy induce hypertriglyceridemia), we studied the role of APOA5 in a population of patients infected by the VIH virus, and we found that in the group of subjects treated with protease inhibitors, carrying the -1131C