Estudo do perfil genético e molecular do sistema calicreína-cininas em pacientes portadores de hipercolesterolemia familiar

• Ano de defesa: 2019
• Autor(a) principal: Bittencourt, Clarissa Azevedo [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/48912/001300002tpmm
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Cininas; Hypercholesterolemia Family; Cardiovascular Diseases; Genetics; Hipercolesterolemia Familiar; Doenças Cardiovasculares; Genética
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7635835; https://repositorio.unifesp.br/handle/11600/59714

Familial hypercholesterolemia is an autosomal dominant genetic disorder characterized by increased serum levels of total cholesterol and low-density lipoprotein cholesterol. Familial hypercholesterolemia is directly related to the development of cardiovascular diseases, such as hypertension, atherosclerosis, myocardial infarction and coronary disease. In this context, the kallikrein-kinin system actively participates in the regulation of cardiovascular system functions, as demonstrated in studies with angiotensin-converting enzyme inhibitors and has cardioprotective effects mediated by the direct release of nitric oxide by endothelium or stimulated by prostaglandins. No study has so far associated the contribution of the kallikrein-kinin system in the modulation of symptoms or in the pathogenesis of familial hypercholesterolemia. Thus, in this work we investigated the genetic profile of the kallikrein-kinin system in patients with familial hypercholesterolemia. The new generation sequencing of eleven genes related to the kallikrein-kinin system were carried out in 102 patients with familial hypercholesterolemia. 22 rare variants were identified, with nine variants classified as pathogenic by in silico predictors; and 14 polymorphisms. Eight of these variants, present in the ACE, KLK1 and KNG1 genes may be candidate variants to be related to systemic arterial hypertension. Despite the limitations of the association between genotype and phenotype, the results obtained in this work open the opportunity to expand knowledge about the possible modulation of the kallikrein-kinin system in the development of cardiovascular diseases, particularly hypertension, in the context of familial hypercholesterolemia.