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

Abstract

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.

Significant association between functional microRNA polymorphisms and coronary heart disease susceptibility: a comprehensive meta-analysis involving 16484 subjects

“…Then, 19 studies including 6 reviews, 12 studies not for focus polymorphisms, and 1 study without available information [22] were excluded. Finally, 12 eligible articles (13 studies) published from 2012 to 2016 were selected in the meta-analysis, including ten studies on microRNA-146a rs2910164 G>C [23–32], seven studies on microRNA-196a2 rs11614913 T>C [23, 26, 27, 29, 31, 33], six publications on microRNA-499 rs3746444 A>G [23, 25, 26, 29, 31, 33], and two studies on microRNA-149 rs71428439 A>G [29, 34], respectively. The process of study selection was shown in Figure 1.…”

“…The process of study selection was shown in Figure 1. Among the retrieved articles, nine articles [23, 24, 26–30, 33, 34] were written in English and three [25, 31, 32] in Chinese. Moreover, two of the studies involved Caucasians [24, 30], and eleven of them were conducted for Asians.…”

“…The advantages of our analysis are as follows. First, our meta-analysis had much larger sample size: we added another six recent studies involving 8,134 subjects which were not part of the previous meta-analysis [23, 24, 27, 29, 31, 32]. Second, sensitivity analyses showed that our results were statistically robust in four genetic models.…”

Association between the miRNA‐149 rs2292832 T>C polymorphism and Kawasaki disease susceptibility in a southern Chinese population

“…To a certain extent, the alteration of rs2292832 T>C in miRNA ‐149 may cause alterations in expression and susceptibility to diseases. For example, Sun et al reported that in a Korean population, some miRNAs and combinations of genotype polymorphisms, such as miRNA‐149 rs2292832 T>C, could contribute to the occurrence of coronary artery disease, a major complication in KD. A study in a Chinese population might obtain similar results.…”

A functional variant of miRNA‐149 confers risk for allergic rhinitis and comorbid asthma in Chinese children

“…Six SNPs located in the pre-miRNA regions of miR-146a (rs2910164, rs57095329 and rs6864584), miR-149 (rs2292832), miR-196a2 (rs11614913) and miR-499 (rs3746444) have been identified, using bioinformatic methods, as common SNPs (Hu et al, 2008), and they are considered the genetic predisposition factors for various inflammation-related diseases (Qi et al, 2013). The combined effects of the environmental factors and miR-149, miR-146a and miR-196a2 polymorphism combinations may contribute to the development of coronary artery disease (CAD; Sung et al, 2016). Furthermore, mir-499 was shown to be involved in autoimmune and inflammatory disease progression.…”