Analysis of genetic markers for cardiovascular disorders in a portuguese population with familial hypercholesterolemia

Tese de mestrado em Biologia (Biologia Humana e Ambiente), apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2009 ; Familial Hypercholesterolemia (FH) is a genetic disorder that leads to an increase in the levels of total and low density lipoprotein cholesterol promoting atherosclerosis (ATH) and premature cardiovascular disease (CVD). Inflammation has been considered to be involved in the pathogenesis of CVD namely the activity of pro-inflammatory cytokines and acute phase proteins. Also, there are other risk factors contributing to the development and progression of ATH and CVD as genetic and oxidative stress markers. We intended to investigate the role of genetic, inflammatory and oxidative biomarkers in the clinical outcome of FH patients and study its putative correlation with CVD. There were selected 41 FH patients with CVD, 91 without CVD and 49 healthy individuals. All individuals were characterized through the determination of the lipid profile (high density lipoprotein, LDL and total cholesterol, triglycerides, apoA, apoB, lipoprotein(a)), measurement of the serum concentration of some inflammatory markers (Cp, haptoglobin and C reactive protein), proinflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha), homocysteine and markers of antioxidant / pro-oxidant status (nitric oxid and oxLDL). The genetic characterization was achieved by studying polymorphisms in the genes encoding for LPL, APOAV, APOCIII, TNF-α, IL-6, MTHFR and NOS, which are thought to be involved in the inflammatory process and the predisposition to CVD. The results showed that the group of FH patients with CVD presented increased total (p<0,001) and LDL cholesterol (p=0,001) and apoB (p<0,001) levels and decreased apoA1 (p=0,021) levels in relation to the FH group without CVD. In the FH group with CVD it was observed the highest oxLDL and the lowest NO concentrations. APOAV-1131C and APOCIII 3238G allele were associated with higher TG levels (p=0,013; p=0,042) in the FH group without CVD. ...