NAMPT (visfatin) and AKT1 genetic variants associate with myocardial infarction

Abstract

Background: High plasma levels of the adipokine NAMPT (or visfatin) have been associated with cardiovascular disease. However experimental data suggest that NAMPT, via Akt signaling, protects the myocardium against hypoxic insults. We studied whether the NAMPT rs1319501, AKT1 rs3730358, p53 rs1042522, Mdm2 rs2279744 or eNOS rs1799983 SNP:s linked to NAMPT and Akt signaling associate with risk of myocardial infarction (MI). Methods: Cases were 828 men and 346 women aged 45-70 who had suffered a first MI. Control individuals, 1062 men and 513 women, were randomly chosen from the study base. We employed unconditional logistic regression analysis. Results: The rs1319501 minor allele associated with MI among women aged 45-60; odds ratio (OR) under a recessive model of inheritance: 2.96 (95% confidence interval [CI] 1.06-8.29). Replication analysis in an independent material yielded OR point estimates in the same direction. The rs3730358 minor allele associated with low MI risk in men aged 45-60 (OR dominant model: 0.72, 95% CI 0.53-0.97), an association completely attenuated by adjusting for inflammatory markers. Conclusions: The NAMPT rs1319501 minor allele associates with increased MI risk in young women. In young men a protective effect of the AKT1 rs3730358 minor allele was suggested, possibly related to an attenuated inflammation. © 2012 Elsevier B.V.