Estudi genètic i epigenètic sobre la dislipèmia aterògena en pacients amb diabetis tipus 2, síndrome metabòlica o diabetis tipus 3

Identifier:  TDX:2615

Handle: https://hdl.handle.net/20.500.11797/TDX2615

Authors:  Oliva Rodríguez, Iris

Abstract:
LDL cholesterol is the main independent risk factor for cardiovascular diseases development. However, approximately a 40% of patients with normal LDL cholesterol levels also present a high cardiovascular risk. This is the case of patients with type 2 diabetes or metabolic syndrome who are characterised by an abnormal lipoprotein profile known as atherogenic dyslipidemia (AD). It has been described a similar abnormal lipoprotein profile in patients with type 3 diabetes, a feature of Alzheimer disease patients. AD courses with high triglycerides levels, normal LDL cholesterol levels and low HDL cholesterol levels. Due to the unaltered LDL cholesterol levels, it could seem that it is not a pathogenic profile, but, the increment of triglycerides levels induces qualitative and quantitative changes in the lipoprotein profile becoming lipoproteins more proatherogenic particles. More specifically, AD is characterised by: an increment in VLDL particles and its large subfraction, an increment of small and dense LDL, a diminution of HDL and an increment of remnant lipoprotein particles. AD presents a high heritability. In this sense, genome complete association studies determined that identified variants only represents a 25-30% of genetic predisposition, what suggests that there are other genetic factors that could influence the lipid profile, such as epigenetic modifications. For these reasons, the aim of this thesis has been determining if genetic and epigenetic factors, alone or in combination, could explain the mechanisms that modulate the genetic predisposition to dyslipidemia related with complex diseases as type 2 diabetes, metabolic syndrome or type 3 diabetes.