Influence of the combination of SNPs on dyslipidemias and lipid parameters

Identifier:  TFG:2166

Handle: https://hdl.handle.net/20.500.11797/TFG2166

Authors:  Cerezuela Filgueras, Nerea

Abstract:
Cardiovascular diseases are one of the biggest problems in developed countries. The increase of circulating lipids is one of the main risk factors for this type of disease. The genetic control of dyslipidemias involves the participation of one or a few causal mutations in some of the key genes for lipid metabolism (in primary dyslipidemias), or the participation of a set of genetic variations in different points of the genome involved in the regulation of circulating lipids together with environmental factors (in secondary dyslipidemias). A population of 480 individuals has been selected. It includes healthy individuals and patients with high cardiovascular risk. In both cases a detailed lipid profile is available. We have selected 45 SNPs located in 25 genes involved in lipid metabolism, inflammatory factors and in the pathogenesis of atherosclerosis. They have been selected in order to find those SNPs associated with the main dyslipidemias and circulating lipids, and which may be good markers for predicting the risk of suffering from lipid disorders and therefore a higher risk of suffering from related diseases. It has been possible to find a relationship between certain SNPs and the most frequent dyslipidemias: 4 SNPs related to isolated hypercholesterolemia; 2 SNPs related to isolated hypertriglyceridemia; 4 SNPs related to combined hyperlipidemia; and 1 with atherogenic dyslipidemia. We have found that the SNPs rs2948080 (in the KAT2B gene), rs540796 and rs562556 (in PCSK9), rs1042034 (in APOB), rs3135506 and rs964184 (in APOA5) and rs4520 (in APOC3) are significantly associated with the concentration of LDL cholesterol and with the number of circulating LDL particles. It has also been observed a dose-dependent effect between the number of alleles of the SNPs studied and the LDL cholesterol concentration.