Efeitos da variante rs2070744 do gene da enzima óxido nítrico sintase endotelial (eNOS) na doença arterial coronariana
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2015-01
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Contini, Verônica
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A Doença arterial coronariana (DAC) é uma doença multifatorial, representado uma das principais causas de morbidade e mortalidade global. Na última década, um grande número de trabalhos sobre a relação do óxido nítrico (ON) e DAC foram publicados. A diminuição do ON no endotélio pode causar disfunção, acelerar a aterosclerose e a progressão das doenças cardiovasculares e vários estudos têm identificado polimorfismos comuns no gene da enzima óxido nítrico sintase endotelial (eNOS), responsável pela biossíntese de ON, os quais podem estar associados a aterosclerose e a doença arterial cardíaca. Objetivo: O objetivo deste estudo foi investigar o papel de dois polimorfismos do gene eNOS (rs2070744 e rs1799983) na DAC. Metodologia: A amostra foi composta de 645 pacientes, maiores de 18 anos, submetidos ao exame de cateterismo cardíaco no Hospital Bruno Born de Lajeado, RS. Foram coletadas amostras de sangue para análises bioquímicas e extração de DNA, que foram realizadas nos Laboratório do Universidade do Vale do Taquari Univates. Todos os pacientes incluídos no estudo assinaram um termo de consentimento livre e esclarecido e, com base em suas características clínicas, foram classificados em um Escore de Risco Global (ERG) de DAC, proposto pela Sociedade Brasileira de Cardiologia. A influência dos polimorfismos em variáveis clínicas foi avaliada através de modelos lineares univariados ou por Kruskal-Wallis. A associação dos genótipos com as variáveis categóricas foi investigada pelo teste do qui-quadrado ou por regressão logística binária. Resultados: De acordo com a pontuação no ERG, 435 pacientes (68%) foram classificados em alto risco, 166 em risco intermediário (26%) e 39 (6%) em baixo risco para a DAC. As frequências alélicas dos polimorfismos investigados no gene eNOS foram 0,69 (G) e 0,31 (T) para a variante rs1799983 e 0,59 (T) e 0,41 (C) para o rs2070744. Não foram detectados efeitos genéticos significativos do polimorfismo rs1799983 nas variáveis clínicas investigadas. Efeitos genéticos do rs2070744 foram encontrados nos valores de colesterol HDL (p=0,002) e na pontuação do ERG (p=0,032). Indivíduos homozigotos TT apresentaram valores de HDL maiores que indivíduos TC e CC e menor pontuação no ERG do que pacientes TC. Na análise categórica também se detectou um aumento do risco no ERG em indivíduos heterozigotos TC, quando comparados aos indivíduos TT (p=0,028). Conclusão: Nossos resultados sugerem que o polimorfismo rs2070744 no gene eNOS está associado com o risco aumentado de DAC na nossa amostra.
Coronary artery disease (CAD) is a multifactorial disease, representing a major cause of morbidity and overall mortality. In the last decade, a large number of studies related to nitric oxide (ON) and CAD have been published. The reduction of ON in the endothelium may cause dysfunction, accelerate the progression of atherosclerosis and cardiovascular diseases and several studies have identified common polymorphisms in the gene of the endothelial nitric oxide synthase enzyme (eNOS), responsible for the biosynthesis of ON, which may be associated with artery atherosclerosis and heart disease. Objective: The objective of this study was to investigate the role of two polymorphisms in the eNOS gene (rs2070744 and rs1799983) in CAD. Methods: The sample consisted of 645 patients submitted to cardiac catheterism in the Hospital Bruno Born, Lajeado, RS. Blood samples were collected for biochemical analyzes and DNA extraction, which were conducted in the Laboratory of the University Center Univates. All patients included in the study signed an informed consent form and, based on their clinical characteristics, were ranked on a Score of Global Risk (SGR) of CAD, proposed by the Brazilian Society of Cardiology. The influence of the polymorphisms on clinical variables was evaluated by univariate linear models or Kruskal-Wallis test. The association between the genotypes and categorical variables was investigated by the chi-square test or by binary logistic regression. Results: According to the score SGR, 435 patients (68%) were classified as high risk, 166 at intermediate risk (26%) and 39 (6%) at low risk for CAD. Allele frequencies of the investigated polymorphisms in eNOS gene were 0.69 (G) and 0.31 (t) for the rs1799983 variant and 0.59 (T) 0.41 (C) for rs2070744. No significant genetic effects were detected for the polymorphism rs1799983 in the clinical variables. Genetic effects of rs2070744 were found in HDL cholesterol (p = 0.002) and in the SGR score (p = 0.032). Individuals homozygous TT had higher HDL levels than individuals TC and CC and lowest score in the SGR than TC patients. In the categorical analysis we also found an increased risk in the SGR for individuals heterozygous TC, when compared to TT subjects (p = 0.028). Conclusion: Our results suggest that the rs2070744 polymorphism in the eNOS gene is associated with increased risk of CAD in our sample.
Coronary artery disease (CAD) is a multifactorial disease, representing a major cause of morbidity and overall mortality. In the last decade, a large number of studies related to nitric oxide (ON) and CAD have been published. The reduction of ON in the endothelium may cause dysfunction, accelerate the progression of atherosclerosis and cardiovascular diseases and several studies have identified common polymorphisms in the gene of the endothelial nitric oxide synthase enzyme (eNOS), responsible for the biosynthesis of ON, which may be associated with artery atherosclerosis and heart disease. Objective: The objective of this study was to investigate the role of two polymorphisms in the eNOS gene (rs2070744 and rs1799983) in CAD. Methods: The sample consisted of 645 patients submitted to cardiac catheterism in the Hospital Bruno Born, Lajeado, RS. Blood samples were collected for biochemical analyzes and DNA extraction, which were conducted in the Laboratory of the University Center Univates. All patients included in the study signed an informed consent form and, based on their clinical characteristics, were ranked on a Score of Global Risk (SGR) of CAD, proposed by the Brazilian Society of Cardiology. The influence of the polymorphisms on clinical variables was evaluated by univariate linear models or Kruskal-Wallis test. The association between the genotypes and categorical variables was investigated by the chi-square test or by binary logistic regression. Results: According to the score SGR, 435 patients (68%) were classified as high risk, 166 at intermediate risk (26%) and 39 (6%) at low risk for CAD. Allele frequencies of the investigated polymorphisms in eNOS gene were 0.69 (G) and 0.31 (t) for the rs1799983 variant and 0.59 (T) 0.41 (C) for rs2070744. No significant genetic effects were detected for the polymorphism rs1799983 in the clinical variables. Genetic effects of rs2070744 were found in HDL cholesterol (p = 0.002) and in the SGR score (p = 0.032). Individuals homozygous TT had higher HDL levels than individuals TC and CC and lowest score in the SGR than TC patients. In the categorical analysis we also found an increased risk in the SGR for individuals heterozygous TC, when compared to TT subjects (p = 0.028). Conclusion: Our results suggest that the rs2070744 polymorphism in the eNOS gene is associated with increased risk of CAD in our sample.
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Palavras-chave
Doença arterial coronariana; Associação genética; Enzima óxido nítrico sintase endotelial; eNOS
Citação
TOFFOLI, Camila Dalacort. Efeitos da variante rs2070744 do gene da enzima óxido nítrico sintase endotelial (eNOS) na doença arterial coronariana. 2015. Dissertação (Mestrado) – Curso de Biotecnologia, Universidade do Vale do Taquari - Univates, Lajeado, jan. 2015. Disponível em: http://hdl.handle.net/10737/794.