Influência de polimorfismos em genes do processo inflamatório na doença arterial coronariana
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2017-06
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Contini, Verônica
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Introdução: A doença arterial coronariana (DAC) é a principal causa de morbidade e mortalidade no mundo, sendo caracterizada como uma doença inflamatória crônica, multifatorial, cuja fisiopatologia é a aterosclerose. Considerando a alta herdabilidade da doença, vários polimorfismos genéticos vêm sendo estudados e associados com o surgimento da DAC e, entre eles, destacam-se variantes nos genes CD14, TLR4, NFKB1 e TNFα, os quais regulam a via de sinalização celular do sistema imune inato e desencadeiam o processo inflamatório na DAC. Objetivo: O objetivo principal deste estudo é verificar a possível associação de polimorfismos nos genes CD14 (rs2569190), TLR4 (rs4986790 e rs4986791), NFKB1 (rs28362491) e TNFα (rs1800629 e rs361525) com a DAC. Metodologia: A amostra foi composta por 707 indivíduos adultos submetidos ao exame de cateterismo cardíaco no Hospital Bruno Born, de Lajeado, RS. Todos os indivíduos assinaram um termo de consentimento livre e esclarecido e responderam a um questionário semiestruturado. Os indivíduos foram classificados entre casos e controles, por um médico cardiologista, com base no seguinte critério: presença de estenose, com comprometimento maior do que 50%, em pelo menos uma das artérias coronárias. Foram também coletadas amostras de sangue periférico para análises bioquímicas e moleculares. A extração de DNA foi realizada pelo método de salting out. Os polimorfismos dos genes CD14, TLR4 e TNFα foram genotipados pelo sistema de discriminação alélica TaqMan, em equipamento de reação em cadeia da polimerase (PCR) em Tempo Real (StepOnePlus®). O polimorfismo rs28362491, no gene NFKB1, foi amplificado através da técnica convencional de PCR. Resultados: Identificamos uma associação dos polimorfismos rs2569190, localizado no gene CD14, e rs28362491, no gene NFKB1, com a DAC. Além disso, foram detectados efeitos dos polimorfismos dos genes TLR4 e TNFα nos níveis glicêmicos e dos polimorfismos nos genes TLR4, NFKB1 e TNFα no perfil lipídico. Conclusão: Nossos achados sugerem a participação de polimorfismos nos genes CD14 e NFKB1 no desenvolvimento da DAC na nossa amostra, corroborando evidências prévias do envolvimento de genes do processo inflamatório nessa patologia.
Introduction: Coronary artery disease (CAD) is the main cause of morbidity and mortality in the world, being characterized as a chronic, multifactorial inflammatory disease, whose pathophysiology is atherosclerosis. Considering the high heritability of the disease, several genetic polymorphisms have been investigated and associated with CAD and, among them, there are variants in the CD14, TLR4, NFKB1 and TNFα genes, which regulate cell signaling pathways of the innate immune system and inflammatory process in CAD. Objective: The main objective of this study is to verify the association beteween polymorphisms in the CD14 (rs2569190), TLR4 (rs4986790 and rs4986791), NFKB1 (rs28362491) and TNFα (rs1800629 and rs361525) genes and CAD. Methods: The sample group was composed of 707 adult individuals, recruited at the time when they were bought in for coronary angiography procedures at the Hemodynamic Center of the Hospital Bruno Born, City of Lajeado, Rio Grande do Sul. The individuals were classified between cases and controls by a cardiologist, based on the following criteria: presence of stenosis, greater than 50% of the luminal diameter, in at least one of the coronary arteries. Peripheral blood samples were also collected for biochemical and molecular analyzes. DNA extraction was performed using the salting out method. The polymorphisms in the CD14, TLR4 e TNFα genes were genotyped by Taqman® allelic discrimination assays. The rs28362491 polymorphism in the NFKB1 gene was amplified by polymerase chain reaction (PCR). Results: We identified an association between the polymorphisms rs2569190, located in the CD14 gene, and rs28362491, located in the NFKB1 gene, and CAD. In addition, there were detected significant effects of TLR4 and TNFα gene polymorphisms on glycemic levels and TLR4, NFKB1 and TNFα gene polymorphisms on the lipid profile. Conclusion: Our findings suggest a role for the polymorphisms in CD14 and NFKB1 genes in CAD susceptibility in our sample, corroborating previous evidence of the envolviment of inflamotory process genes in this patology.
Introduction: Coronary artery disease (CAD) is the main cause of morbidity and mortality in the world, being characterized as a chronic, multifactorial inflammatory disease, whose pathophysiology is atherosclerosis. Considering the high heritability of the disease, several genetic polymorphisms have been investigated and associated with CAD and, among them, there are variants in the CD14, TLR4, NFKB1 and TNFα genes, which regulate cell signaling pathways of the innate immune system and inflammatory process in CAD. Objective: The main objective of this study is to verify the association beteween polymorphisms in the CD14 (rs2569190), TLR4 (rs4986790 and rs4986791), NFKB1 (rs28362491) and TNFα (rs1800629 and rs361525) genes and CAD. Methods: The sample group was composed of 707 adult individuals, recruited at the time when they were bought in for coronary angiography procedures at the Hemodynamic Center of the Hospital Bruno Born, City of Lajeado, Rio Grande do Sul. The individuals were classified between cases and controls by a cardiologist, based on the following criteria: presence of stenosis, greater than 50% of the luminal diameter, in at least one of the coronary arteries. Peripheral blood samples were also collected for biochemical and molecular analyzes. DNA extraction was performed using the salting out method. The polymorphisms in the CD14, TLR4 e TNFα genes were genotyped by Taqman® allelic discrimination assays. The rs28362491 polymorphism in the NFKB1 gene was amplified by polymerase chain reaction (PCR). Results: We identified an association between the polymorphisms rs2569190, located in the CD14 gene, and rs28362491, located in the NFKB1 gene, and CAD. In addition, there were detected significant effects of TLR4 and TNFα gene polymorphisms on glycemic levels and TLR4, NFKB1 and TNFα gene polymorphisms on the lipid profile. Conclusion: Our findings suggest a role for the polymorphisms in CD14 and NFKB1 genes in CAD susceptibility in our sample, corroborating previous evidence of the envolviment of inflamotory process genes in this patology.
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Sistema imune inato; CD14; TLR4; NFKB1; TNFα
Citação
WÜNSCH, Camile. Influência de polimorfismos em genes do processo inflamatório na doença arterial coronariana. 2016. Dissertação (Mestrado) – Curso de Biotecnologia, Universidade do Vale do Taquari - Univates, Lajeado, 19 dez. 2016. Disponível em: http://hdl.handle.net/10737/1581.