Caracterização Bioquímica e Molecular da Hipercolesterolemia Familiar na Região Norte e Centro de Portugal

• Main Author: Freitas, Ana Isabel da Costa
• Publication Date: 2011
• Format: Master thesis
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: http://hdl.handle.net/10400.18/479
• topic: Doenças Cardiovasculares; Hipercolesterolemia Familiar; Colesterol; Lipoproteínas de Baixa Densidade; Receptor das LDL; Mutações Genéticas e Diagnóstico Precoce; Doenças Cardio e Cérebro-vasculares

Familial Hypercholesterolemia (FH) is an autosomal dominant genetic disorder and one of the most common genetic disorders in Europe and often under-diagnosed. The FH phenotype is characterized mainly by increased levels of total cholesterol (TC) and cholesterol in low-density lipoproteins (c-LDL) as well as the development of premature coronary heart disease and atherosclerosis. This condition is often caused by mutations in the Low-Density Lipoproteins Receptor (LDLR) gene however mutations in the Apolipoprotein B (ApoB) gene and Proprotein convertase subtilisin/kexin type 9 (PCSK9) gene are also described as disease causing. The biochemical and molecular characterization of FH in patients from northern and central regions of Portugal was the purpose of this work. The study was based on molecular analysis of the LDLR gene and APOB gene by PCR amplification and direct sequencing. Were referred to the Portuguese Familial Hypercholesterolemia Study (EPHF), 34 individuals born in north or central region of Portugal, however 7 (20.6%) had no criteria for clinical diagnosis of FH. 17 (63%) of 27 index cases studied, were children (_ 16 years). The values of TC and c-LDL in the pediatric group were 249.4 ± 25.6 mg /dL and 173.8 ± 28.0 mg /dL, respectively. In the adult population these values were 308.0 ± 21.9 mg /dL and 218.5 ± 15.6 mg /dL. The genetic cause of hypercholesterolemia was determined in 29.6% of individuals. 7 genetic alterations were identified in the LDLR gene and only 1 in the APOB gene. Of the founded mutations, 3 are not yet described. This study highlights the importance of early diagnosis and cardiovascular prevention, enabling the introduction of therapeutic measures earlier and/or aggressive in both index cases and relatives, identified genetically with FH.