Hsa-mir-499 rs3746444 T/C Polymorphism is Associated with Increased Risk of Coronary Artery Disease in a Chinese Population

Acta Cardiol Sin. 2017 Jan;33(1):34-40. doi: 10.6515/acs20160303a.

Abstract

Background: Coronary artery disease (CAD) is a complex disease resulting from a combination of environmental and genetic factors. We hypothesized that polymorphisms hsa-mir-499 rs3746444 T/C, IRAK1 rs3027898 C/A and RANKL rs7984870 C/G might contribute to CAD susceptibility.

Methods: We studied the association between the three polymorphisms and the risk of CAD in a Chinese population using 435 CAD patients and 480 controls. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used to perform the genotyping, and the differences were analysed.

Results: When the hsa-mir-499 rs3746444 TT homozygote genotype was used as the reference group, the TC, CC or TC/CC genotypes were associated with a significantly increased risk of CAD [TC vs. TT: adjusted odds ratio (OR) 1.41, 95% confidence interval (CI) 1.02-1.94, p = 0.04; CC vs. TT: adjusted OR 3.14, 95% CI 1.77-5.56, p < 0.001; CC/TC vs. TT: adjusted OR 1.68, 95% CI 1.25-2.26, p < 0.001). In the recessive model, when the hsa-mir-499 rs3746444 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased risk of CAD (adjusted OR 2.87, 95% CI 1.63-5.04, p < 0.001). Risk factors such as diabetes mellitus (DM), hypertension, smoking and low high-density ipoprotein cholesterol (HDL-c) were also associated with a significantly increased risk for CAD. Logistic regression analyses revealed that IRAK1 rs3027898 C/A and RANKL rs7984870 C/G polymorphisms were not associated with risk of CAD.

Conclusions: These findings suggested that the functional polymorphism hsa-mir-499 rs3746444 T/C is associated with CAD susceptibility.

Keywords: Cardiovascular disease; Hsa-mir-499; Molecular epidemiology; Polymorphisms.