Estudo do polimorfismo genético da óxido nítrico sintetase endotelial em pacientes portadores de hipertensão arterial com e sem síndrome metabólica
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Data
2024-05-30
Autores
Penedo, Tamara Rampanelli [UNIFESP]
Orientadores
Batista, Marcelo Costa [UNIFESP]
Tipo
Dissertação de mestrado
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Introdução: A obesidade visceral, componente central da Síndrome Metabólica (SM), representa a base fisiopatológica que justifica a epidêmica ocorrência de doença cardiovascular (DCV) observada nessa condição e é concebida como um estado inflamatório. O polimorfismo 4b/a do gene da Óxido Nítrico Sintetase endotelial (eNOS) tem sido alvo de extensa pesquisa, evidenciando sua associação com a redução da produção de óxido nítrico (NO) e o desenvolvimento de disfunção endotelial (DE). Nesse contexto, a microalbuminúria e a dimetil arginina assimétrica (ADMA) assumem papel relevante como marcadores de inflamação e DE, constituindo fatores de risco para condições como Hipertensão Arterial Sistêmica (HAS), Diabetes Mellitus (DM) e Doença Renal Crônica (DRC). Dentro desse conceito, a partir de uma plataforma assistencial desenvolvida no Centro de Hipertensão e Metabologia Cardiovascular da Fundação Oswaldo Ramos – Universidade Federal de São Paulo, o objetivo deste estudo foi identificar a prevalência do polimorfismo 4b/a do gene 27pb no íntron 4 do gene da eNOS em indivíduos portadores de HAS estratificados em função da presença da SM. Materiais e métodos: Em estudo prospectivo foram incluídos 208 pacientes hipertensos, submetidos à análise do Polimorfismo da eNOS (4a/b). Foram analisadas a presença da SM e seus componentes, além de associações entre o polimorfismo e DE, definidas pelas medianas de ADMA e microalbuminúria. Resultados: A população da coorte foi predominantemente feminina, na sua maioria de etnia branca, com idade média de 59,7 anos, sendo todos portadores de hipertensão essencial. Destes pacientes 59,7% apresentavam SM e mais de 90% eram portadores do alelo b. Nos pacientes com SM no início do seguimento observamos que o High Density Lipoproteins (HDL) foi inferior nos pacientes sem DE comparado com os portadores da DE; já a albuminúria e o Proteína C – reativa (PCR) foram superiores nos pacientes sem DE em relação aos portadores da DE. Ao final do seguimento observamos que os níveis de HDL foram menores nos pacientes com DE em comparação aos sem DE e a albuminúria foi maior nos pacientes sem DE quando comparada aos pacientes com DE. Na análise que considerou os pacientes portadores do alelo A verificamos um incremento significativo apenas na visita final do seguimento na pressão arterial diastólica (PAD) nos pacientes sem DE; o Very Low Density Lipoprotein (VLDL) e a albuminúria foi maior nos pacientes com DE em comparação aos sem DE. Na visita inicial, os indivíduos portadores do alelo B apresentaram os níveis de VLDL, triglicerídeos (TG) e o PCR foram elevados nos pacientes com DE em comparação com pacientes sem DE. Na visita final os níveis de HDL foram mais baixos nos pacientes com DE e os níveis de VLDL, o TG, a cintura abdominal e a albuminúria foram mais altos nos pacientes com DE. A análise por regressão logística binária demonstrou que a presença de alelo A associou-se de maneira independente à ocorrência de DE nos pacientes com SM e tal associação não foi encontrada nos pacientes sem SM. Conclusão: Em uma coorte de pacientes portadores de Hipertensão arterial e SM, a presença do alelo A do polimorfismo 4 a/b da eNOS associou-se à ocorrência de DE ao final do seguimento.
Introduction: Visceral obesity, a central component of Metabolic Syndrome (MetS), represents the pathophysiological basis that justifies the epidemic occurrence of cardiovascular disease (CVD) observed in this condition and is conceived as na inflammatory state. The 4b/a polymorphism of the eNOS gene has been the subject of extensive research, evidencing its association with reduced NO production and the development of endothelial dysfunction. In this context, microalbuminuria and asymmetric dimethylarginine (ADMA) play a relevant role as markers of inflammation and endothelial dysfunction (ED), constituting risk factors for conditions such as Systemic Arterial Hypertension (SAH), Diabetes Mellitus (DM), and Chronic Kidney Disease (CKD). Within this concept, based on a care platform developed at the Hypertension and Cardiovascular Metabolism Center of the Oswaldo Ramos Foundation – Federal University of São Paulo, the aim of this study was to identify the prevalence of the 4b/a polymorphism of the 27bp gene in intron 4 of the Endothelial Nitric Oxide Synthase (eNOS) gene in individuals with SAH stratified according to the presence of MetS. Materials and methods: In a prospective study, 208 hypertensive patients were included, undergoing analysis of the eNOS Polymorphism (4a/b). The presence of MetS and its components were analyzed, as well as associations between polymorphism and ED, defined by ADMA and microalbuminuria medians. Results: The cohort population was predominantly female, mostly of white ethnicity with a mean age of 59.7 years, all having essential hypertension. Of these patients, 59.7% had MetS, and over 90% carried the b allele. In patients with MetS at baseline, we observed that HDL was lower in patients without ED compared to those with ED; meanwhile, albuminuria and CRP were higher in patients without ED compared to those with ED. At the end of follow-up, HDL levels were lower in patients with ED compared to those without ED, and albuminuria was higher in patients without ED compared to those with ED. In the analysis considering patients carrying the A allele, a significant increase was observed only at the final follow-up visit in DBP in patients without ED; VLDL and albuminuria were higher in patients with ED compared to those without ED. At the initial visit, individuals carrying the B allele had elevated levels of VLDL, TG, and CRP in patients with ED compared to those without ED. At the final visit, HDL levels were lower in patients with ED, and VLDL levels, TG, waist circumference, and albuminuria were higher in patients with ED. Binary logistic regression analysis demonstrated that the presence of the A allele was independently associated with the occurrence of ED in patients with MetS, and this association was not found in patients without MetS. Conclusion: In a cohort of patients with arterial hypertension and MetS, the presence of the A allele of the 4a/b polymorphism of eNOS was associated with the occurrence of ED at the end of follow-up.
Introduction: Visceral obesity, a central component of Metabolic Syndrome (MetS), represents the pathophysiological basis that justifies the epidemic occurrence of cardiovascular disease (CVD) observed in this condition and is conceived as na inflammatory state. The 4b/a polymorphism of the eNOS gene has been the subject of extensive research, evidencing its association with reduced NO production and the development of endothelial dysfunction. In this context, microalbuminuria and asymmetric dimethylarginine (ADMA) play a relevant role as markers of inflammation and endothelial dysfunction (ED), constituting risk factors for conditions such as Systemic Arterial Hypertension (SAH), Diabetes Mellitus (DM), and Chronic Kidney Disease (CKD). Within this concept, based on a care platform developed at the Hypertension and Cardiovascular Metabolism Center of the Oswaldo Ramos Foundation – Federal University of São Paulo, the aim of this study was to identify the prevalence of the 4b/a polymorphism of the 27bp gene in intron 4 of the Endothelial Nitric Oxide Synthase (eNOS) gene in individuals with SAH stratified according to the presence of MetS. Materials and methods: In a prospective study, 208 hypertensive patients were included, undergoing analysis of the eNOS Polymorphism (4a/b). The presence of MetS and its components were analyzed, as well as associations between polymorphism and ED, defined by ADMA and microalbuminuria medians. Results: The cohort population was predominantly female, mostly of white ethnicity with a mean age of 59.7 years, all having essential hypertension. Of these patients, 59.7% had MetS, and over 90% carried the b allele. In patients with MetS at baseline, we observed that HDL was lower in patients without ED compared to those with ED; meanwhile, albuminuria and CRP were higher in patients without ED compared to those with ED. At the end of follow-up, HDL levels were lower in patients with ED compared to those without ED, and albuminuria was higher in patients without ED compared to those with ED. In the analysis considering patients carrying the A allele, a significant increase was observed only at the final follow-up visit in DBP in patients without ED; VLDL and albuminuria were higher in patients with ED compared to those without ED. At the initial visit, individuals carrying the B allele had elevated levels of VLDL, TG, and CRP in patients with ED compared to those without ED. At the final visit, HDL levels were lower in patients with ED, and VLDL levels, TG, waist circumference, and albuminuria were higher in patients with ED. Binary logistic regression analysis demonstrated that the presence of the A allele was independently associated with the occurrence of ED in patients with MetS, and this association was not found in patients without MetS. Conclusion: In a cohort of patients with arterial hypertension and MetS, the presence of the A allele of the 4a/b polymorphism of eNOS was associated with the occurrence of ED at the end of follow-up.
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Citação
PENEDO, Tamara Rampinelli. Estudo do polimorfismo genético da óxido nítrico sintetase endotelial em pacientes portadores de hipertensão arterial com e sem síndrome metabólica. 2024. 72 f. Dissertação (Mestrado em Nefrologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2024.