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
1 Federal University of São Paulo (UNIFESP), Diabetes Center, Rua Pedro de Toledo 910, São Paulo CEP 04039-002, SP Brazil
2 CEDEBA, Av. Antonio Carlos Magalhães, S/N, Salvador CEP 41820-000, BA, Brazil
3 Cardiology Unit, UNIFESP, Rua Napoleão de Barros, 715 CEP, Térreo. São Paulo 04039-002, SP Brazil
4 Research Division, Joslin Diabetes Center, One Joslin Place Boston 02215, MA, USA
5 INSERM, Research Unit 695, 16 rue Henri Huchard, Paris 75018, France
Cardiovascular Diabetology 2013, 12:119 doi:10.1186/1475-2840-12-119Published: 22 August 2013
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).
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).
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.
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.