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Estudo da interação entre moduladores da homeostasia do ferro na Insuficiência Cardíaca
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Resumo(s)
A insuficiência cardíaca (IC) define o estado patológico do coração resultante da incapacidade
de bombear o sangue de forma a fornecer as condições necessárias para o metabolismo humano manter
o seu equilíbrio nas funções diárias. Estudos anteriores verificaram que diversos parâmetros genéticos,
bioquímicos e/ou hematológicos, envolvidos no metabolismo do ferro, são possíveis moduladores do
fenótipo da IC.
Esta dissertação tem como objetivo estudar a contribuição de três genes e de sete parâmetros
bioquímicos envolvidos na homeostasia do ferro, no desenvolvimento de IC e na forma como esta se
apresenta - Fração de Ejeção (FE). O estudo é suportado por 301 amostras no grupo de indivíduos com
IC, divididas em duas subcategorias consoante a sua FE, e 361 amostras no grupo controlo.
Recorreu-se à técnica de PCR-ARMS Multiplex para a genotipagem dos polimorfismos
rs1800562 - C282Y e rs1799945 - H63D (HFE), e à técnica de Endpoint Genotyping para os
polimorfismos rs1439816 e rs2304704 (SLC40A1) e rs855791 (TMPRSS6). Os parâmetros
hematológicos e bioquímicos estudados foram o ferro sérico, a ferritina, a saturação da transferrina, a
Hb, o VGM, o RDW e a CTFF.
Nesta dissertação pode destacar-se a presença de anemia ferropénica na população de IC, bem
como o risco da presença do alelo C e dos genótipos CG (rs1439816 – SLC40A1) e AA (rs855791 -
TMPRSS6), para o desenvolvimento de ICFEp nos homens. De salientar ainda, a proteção conferida
pelo genótipo AG (rs2304704 - SLC40A1) no desenvolvimento de ICFEnp no geral, e só nas mulheres.
Verificou-se ainda que a relação epistática entre os genótipos CG (rs1439816) e AA (rs855791)
aumentou o risco de desenvolvimento de IC.
Por fim, constatou-se que os três genes em estudo estão associados ao desenvolvimento de IC,
como também contribuíram para a modulação de um ou mais parâmetros bioquímicos e hematológicos
importantes na apresentação da doença.
Heart failure (HF) defines the pathological state of the heart resulting from the inability to pump blood in order to provide the necessary conditions for the human metabolism to maintain its balance in daily functions. Previous studies have shown that several genetic, biochemical and/or hematological parameters involved in iron metabolism are possible modulators of the HF phenotype. This dissertation aims to study the contribution of three genes and seven biochemical parameters involved in iron homeostasis, in the development of HF and the form it is presented - Ejection Fraction (EF). This study is supported by 301 samples in the group of individuals with HF, divided into two subcategories according to their EF and 361 samples in the control group. The PCR-ARMS Multiplex technique was used for genotyping the polymorphisms rs1800562 - C282Y and rs1799945 - H63D (HFE), and the Endpoint Genotyping for the polymorphisms rs1439816 and rs2304704 (SLC40A1) and rs855791 (TMPRSS6). The hematological and biochemical parameters studied were serum iron, ferritin, transferrin saturation, Hb, MCV, RDW and TIBC. In this dissertation we can highlight the presence of ferropenic anemia in the HF population, as well as the risk of the presence of the allele C and the genotypes CG (rs1439816 - SLC40A1) and AA (rs855791 - TMPRSS6), for the development of HFpEF in men. Also remarkable is the protection conferred by the genotype AG (rs2304704 - SLC40A1) in the development of HFnpEF in general, and only in women. It was also found that the epistatic relationship between CG (rs1439816) and AA (rs855791) increased the risk of developing HF. Finally, it was found that the three genes under study are associated with the development of HF, as well as contributed to the modulation of one or more important biochemical and hematological parameters in the presentation of the disease.
Heart failure (HF) defines the pathological state of the heart resulting from the inability to pump blood in order to provide the necessary conditions for the human metabolism to maintain its balance in daily functions. Previous studies have shown that several genetic, biochemical and/or hematological parameters involved in iron metabolism are possible modulators of the HF phenotype. This dissertation aims to study the contribution of three genes and seven biochemical parameters involved in iron homeostasis, in the development of HF and the form it is presented - Ejection Fraction (EF). This study is supported by 301 samples in the group of individuals with HF, divided into two subcategories according to their EF and 361 samples in the control group. The PCR-ARMS Multiplex technique was used for genotyping the polymorphisms rs1800562 - C282Y and rs1799945 - H63D (HFE), and the Endpoint Genotyping for the polymorphisms rs1439816 and rs2304704 (SLC40A1) and rs855791 (TMPRSS6). The hematological and biochemical parameters studied were serum iron, ferritin, transferrin saturation, Hb, MCV, RDW and TIBC. In this dissertation we can highlight the presence of ferropenic anemia in the HF population, as well as the risk of the presence of the allele C and the genotypes CG (rs1439816 - SLC40A1) and AA (rs855791 - TMPRSS6), for the development of HFpEF in men. Also remarkable is the protection conferred by the genotype AG (rs2304704 - SLC40A1) in the development of HFnpEF in general, and only in women. It was also found that the epistatic relationship between CG (rs1439816) and AA (rs855791) increased the risk of developing HF. Finally, it was found that the three genes under study are associated with the development of HF, as well as contributed to the modulation of one or more important biochemical and hematological parameters in the presentation of the disease.
Descrição
Tese de mestrado, Biologia Humana e Ambiente , 2024, Universidade de Lisboa, Faculdade de Ciências
Palavras-chave
Insuficiência Cardíaca Metabolismo do Ferro Estudos de Associação Teses de mestrado - 2024