HMGA1 is a novel candidate gene for myocardial infarction susceptibility

Abstract

Background: Acute Myocardial infarction (AMI), a leading cause of morbidity and mortality worldwide, is a dreadful acute complication of coronary atherosclerosis. Type 2 diabetes mellitus (T2DM) is associated with an increased risk of developing AMI. The architectural transcription factor high-mobility-group AT-hook 1 (HMGA1) has been involved in atherosclerosis, plaque formation, inflammation, and in the pathogenesis of insulin resistance and T2DM. An association of the HMGA1 rs146052672 variant with T2DM has been recently reported. Thus, our aim was to evaluate whether this variant was also associated with AMI.

Methods and results: In a case-control study from Calabria (Southern Italy), we enrolled 254 consecutive, unrelated, patients with first diagnosis of AMI, and 508 age, sex-matched controls. Genotyping of the rs146052672 was performed using the TaqMan allelic discrimination method. We found that this variant was present in 7.9% of AMI patients and in 3.1% of controls (p=0.003). Multiple logistic regression confirmed that the rs146052672 was significantly associated with AMI (OR=2.54; p=0.002), and this association was independent of classical cardiovascular risk factors such as gender, hypertension, obesity and T2DM (for all, p<0.05).

Conclusions: Our findings demonstrate that a relationship exists between the HMGA1 rs146052672 variant and AMI, suggesting that defects at the HMGA1 locus may play a pathogenetic role in AMI, in the absence of T2DM and other cardiovascular risk factors.

Keywords: Acute myocardial infarction; Diabetes; Polymorphism; Risk factors.