Associação entre níveis circulantes de nicotinamida fosforribosiltransferase (NAMPT/visfatina) e do polimorfismo frequente rs9770242 da região promotora do gene NAMPT com doença coronariana
Data
2014
Autores
Saddi-Rosa, Pedro 
Orientadores
Reis, André Fernandes
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Diabetes mellitus tipo 2 (DM2) e doenca cardiovascular (DCV) sao doencas associadas a elevada morbi-mortalidade no Brasil e no mundo. Apesar dos avancos no conhecimento e controle de fatores de risco classicos como hipertensao, dislipidemia e tabagismo, ainda permanece um risco residual relevante, o que evidencia a importancia de ampliar as intervencoes de prevencao primaria e secundaria, bem como buscar novos marcadores e fatores de risco cardiovascular. Nicotinamida fosforribosiltransferase (NAMPT) e uma proteina que apresenta efeitos enzimaticos e de citoquina podendo estar relacionada a DCV e DM2. Na presente tese, testamos esta possivel associacao e apresentamos dois artigos resumidos a seguir. No artigo de revisao oVisfatin, glucose metabolismo and vascular disease: a review of evidenceo (Saddi-Rosa P e cols; Diabetol Metab Syndr. 2010; 2:21) discutimos os dados da literatura sobre NAMPT e diversas patologias e condicoes medicas de interesse. Discutimos as associacoes dos niveis sericos de NAMPT com fenotipos metabolicos como aterosclerose, resistencia a insulina, DM2, obesidade e sindrome metabolica. Fizemos tambem uma revisao sobre variacoes geneticas do NAMPT e suas possiveis interacoes com estes fenotipos. Apresentamos no artigo oAssociation of circulating levels of nicotinamide phosphoribosyltransferase (NAMPT/Visfatin) and of a frequent polymorphism in the promoter of the NAMPT gene with coronary artery disease in diabetic and non-diabetic subjectso (Saddi-Rosa P e cols; Cardiovasc Diabetol. 2013; 12: 119) os dados de correlacao de doenca arterial coronariana (DAC) e parametros metabolicos, com os niveis sericos de NAMPT e com o polimorfismo rs9770242 do gene NAMPT, em uma populacao de alto risco cardiovascular. Em pacientes diabeticos, encontramos associacao positiva dos niveis sericos de NAMPT com DAC u 5,27±2,93ng/ml vs. 4,43±2,94ng/ml, p=0.006 (media ± DP). Ja em individuos nao diabeticos, niveis sericos mais elevados de NAMPT associaram-se a um melhor perfil metabolico (IMC, HbA1c, LDL, triglicerides mais baixos e adiponectina mais elevada). Adicionalmente, o polimorfismo rs9770242 associou-se positivamente com DAC (OR=1,46, 95% IC 1,06-2,01, p=0,02) mas este achado nao foi replicado em outra populacao. Nossos resultados confirmam dados da literatura que sugerem uma associacao positiva entre niveis sericos de NAMPT e DAC. Estudos adicionais sao necessarios para estabelecer o papel direto ou indireto de NAMPT na genese da DAC e em fenotipos associados, sobretudo no contexto do DM2. Torna-se necessaria a replicacao da associacao encontrada em nosso estudo em outras populacoes, com casuisticas maiores. Tambem sao necessarios estudos geneticos com a observacao de haplotipos e analises funcionais do gene NAMPT
Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) are diseases associated with high morbidity and mortality in Brazil and worldwide. Despite advances in knowledge and in the control of classic risk factors such as hypertension, dyslipidemia and smoking, there remains a significant residual risk, which highlights the importance of expanding interventions for primary and secondary prevention as well as seeking new cardiovascular markers and risk factors. Nicotinamide phosphoribosyltransferase (NAMPT) is a protein exhibiting enzymatic and cytokine effects which may be related to cardiovascular disease and T2DM. In this thesis, we test this possible association and present two articles summarized below. In the review article "Visfatin, glucose metabolism and vascular disease: a review of evidence" (Saddi-Rosa P et al; Diabetol Metab Syndr. 2010; 2:21). We discuss the data on NAMPT and various diseases and medical conditions of interest. We discuss the associations of serum levels of NAMPT with metabolic phenotypes such as atherosclerosis, insulin resistance, T2DM, obesity and metabolic syndrome. We also reviewed the literature of NAMPT gene variations and their possible interactions with these phenotypes. We present in the article "Association of circulating levels of nicotinamide phosphoribosyltransferase (NAMPT/Visfatin) and of a frequent polymorphism in the promoter of the NAMPT gene with coronary artery disease in diabetic and non-diabetic subjects" (Saddi-Rosa P et al ; Cardiovasc Diabetol. 2013; 12:119) the correlation data of coronary artery disease (CAD) and metabolic parameters with serum levels of NAMPT and with the rs9770242 polymorphism of the NAMPT gene in a population at high cardiovascular risk. In diabetic patients, a positive correlation of serum levels of NAMPT with CAD - 5.27±2.93ng/ml vs. 4.43±2.94ng/ml, p=0.006 (mean±SD). On the other hand, in non-diabetic subjects, higher serum levels of NAMPT were associated with a better metabolic profile (BMI, HbA1c, LDL, lower triglycerides and higher adiponectin). Additionally, the polymorphism rs9770242 was positively associated with CAD (OR=1.46, 95 % CI 1.06 to 2.01, p = 0.02) but this finding was not replicated in another population.
Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) are diseases associated with high morbidity and mortality in Brazil and worldwide. Despite advances in knowledge and in the control of classic risk factors such as hypertension, dyslipidemia and smoking, there remains a significant residual risk, which highlights the importance of expanding interventions for primary and secondary prevention as well as seeking new cardiovascular markers and risk factors. Nicotinamide phosphoribosyltransferase (NAMPT) is a protein exhibiting enzymatic and cytokine effects which may be related to cardiovascular disease and T2DM. In this thesis, we test this possible association and present two articles summarized below. In the review article "Visfatin, glucose metabolism and vascular disease: a review of evidence" (Saddi-Rosa P et al; Diabetol Metab Syndr. 2010; 2:21). We discuss the data on NAMPT and various diseases and medical conditions of interest. We discuss the associations of serum levels of NAMPT with metabolic phenotypes such as atherosclerosis, insulin resistance, T2DM, obesity and metabolic syndrome. We also reviewed the literature of NAMPT gene variations and their possible interactions with these phenotypes. We present in the article "Association of circulating levels of nicotinamide phosphoribosyltransferase (NAMPT/Visfatin) and of a frequent polymorphism in the promoter of the NAMPT gene with coronary artery disease in diabetic and non-diabetic subjects" (Saddi-Rosa P et al ; Cardiovasc Diabetol. 2013; 12:119) the correlation data of coronary artery disease (CAD) and metabolic parameters with serum levels of NAMPT and with the rs9770242 polymorphism of the NAMPT gene in a population at high cardiovascular risk. In diabetic patients, a positive correlation of serum levels of NAMPT with CAD - 5.27±2.93ng/ml vs. 4.43±2.94ng/ml, p=0.006 (mean±SD). On the other hand, in non-diabetic subjects, higher serum levels of NAMPT were associated with a better metabolic profile (BMI, HbA1c, LDL, lower triglycerides and higher adiponectin). Additionally, the polymorphism rs9770242 was positively associated with CAD (OR=1.46, 95 % CI 1.06 to 2.01, p = 0.02) but this finding was not replicated in another population.
Descrição
Citação
SADDI-ROSA, Pedro. Associação entre níveis circulantes de nicotinamida fosforribosiltransferase (NAMPT/visfatina) e do polimorfismo frequente rs9770242 da região promotora do gene NAMPT com doença coronariana. 2014. 82 f. Tese (Doutorado em Ciências) - Escola Paulista de Medicina, Universidade Federal de São Paulo. São Paulo, 2014.