miRNA polymorphisms (miR-146a, miR-149, miR-196a2 and miR-499) are associated with the risk of coronary artery disease

Small non-coding microRNAs (miRNAs) are not only important for heart and vascular development but are also important in cardiovascular pathophysiology and diseases, such as ischemia and atherosclerosis-related diseases. However, the effect of miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms on coronary artery disease (CAD) susceptibility remain unknown. The aim of the present study was to examine the genotype frequencies of miR-146a, miR-149, miR-196a2 and miR-499 polymorphisms in patients with CAD, and assess their clinical applications for diagnosing and monitoring CAD. Using polymerase chain reaction-amplified DNA, microRNA polymorphisms were analyzed in 522 patients with CAD and 535 control subjects. The miR-149 rs2292832 C>T and miR-196a2 rs11614913 T>C polymorphisms were shown to be significantly associated with CAD prevalence. In subgroup analyses according to disease severity, the miR-146a rs2910164GG genotype was significantly associated with CAD risk in the stent 2 group. In addition, miR-146aG/-149T/-196a2C/-499 G allele combination was significantly associated with CAD prevalence (G-T-C-G and G-C-C-G of miR-146a/-149/-196a2/-499). The combination genotypes of miR-146aGG/149TC+CC and miR-149CC/196a2TC were significantly associated with CAD incidence. In subgroup analyses, miR-146a rs2910164 C>G increased the risk of developing CAD in non-smoking, hypertensive and nondiabetic subgroups. Furthermore, miR-149 rs2292832 C>T and miR-196a2 rs11614913 T>C was shown to increase CAD risk in females and patients aged >63 years old. The miR-149T allele, miR-196a2C allele and miR-146aG/-149T/-196a2C/-499 G allele combination were associated with CAD pathogenesis. The combined effects of environmental factor and genotype combination of miRNA polymorphisms may contribute to CAD prevalence.