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

Abstract

Background: Nicotinamide phosphoribosyltransferase (NAMPT) is the limiting enzyme in one of pathways of synthesis of Nicotinamide Adenine Dinucleotide, a redox coenzyme. NAMPT is considered as an insulin-mimetic factor and a potential regulatory factor in inflammatory and immune processes. Associations of circulating NAMPT levels with cardiovascular disease (CVD) and insulin resistance have been reported. We investigated association of circulating NAMPT levels and the rs9770242 NAMPT gene polymorphism with coronary artery disease (CAD).Methods: We studied 594 Brazilian subjects undergoing a coronary angiography (49% of whom had type 2 diabetes). CAD, defined as stenosis greater than 50% in one major coronary vessel or branch, was observed in 68% of subjects. Genetic studies were also performed in 858 North-American Non-Hispanic White subjects with type 2 diabetes (49% with CAD).Results: We observed an interaction between glycemic and CAD status on the comparison of NAMPT levels by CAD status. NAMPT levels were higher in type 2 diabetic patients with CAD as compared to those without CAD: 5.27 +/- 2.93 ng/ml vs. 4.43 +/- 2.94 ng/ml, p = 0.006 (mean +/- SD). NAMPT levels were not significantly different in non-diabetic subjects with or without CAD. the T-allele of rs9770242 was associated with CAD in the Brazilian cohort (OR 1.46, 95% CI 1.06 - 2.01, p = 0.02) while no association was observed in the North-American cohort.Conclusions: Our data suggest that circulating NAMPT levels are associated with CAD in type 2 diabetic patients. NAMPT rs9770242 polymorphism may be associated with CAD in some populations.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fed Univ São Paulo UNIFESP, Ctr Diabet, BR-04039002 São Paulo, BrazilCEDEBA, BR-41820000 Salvador, BA, BrazilUniversidade Federal de São Paulo, Cardiol Unit, BR-04039002 São Paulo, BrazilJoslin Diabet Ctr, Div Res, Boston, MA 02215 USAUniv Paris 07, INSERM, Res Unit 695, F-75018 Paris, FranceFed Univ São Paulo UNIFESP, Ctr Diabet, BR-04039002 São Paulo, BrazilUniversidade Federal de São Paulo, Cardiol Unit, BR-04039002 São Paulo, BrazilFAPESP: 2008/10209-6Web of Scienc