Potential Impact of MicroRNA-423 Gene Variability in Coronary Artery Disease

Abstract

Aim: Studies have evaluated the association of miRNA-423 C>A genotyping with the susceptibility to various diseases such cancers, atherosclerosis and inflammatory bowel disease but the results were contradictory. However, no studies have reported the association between miRNA-423 rs6505162 C>A polymorphism and susceptibility of coronary artery disease. MicroRNAs regulate expression of multiple genes involved in atherogenesis. Therefore, we investigated the association of microRNA-423C>T gene variations with susceptibility to coronary artery disease. Methodology: This study was conducted on 100 coronary artery disease patients and 117 matched healthy controls. The genotyping of the microRNA-423 rs6505162C>A was performed by using Amplification refractory mutation system PCR method (ARMS-PCR). Results: A significant difference was observed in the genotype distribution among the coronary artery disease cases and sex-matched healthy controls (P=0.048). The frequencies of all three genotypes CC, CA, AA reported in the patient’s samples were 55%, 41% and 4% and in the healthy controls samples were 55%, 41% and 4% respectively. Our findings showed that the microRNA-423 C>A variant was associated with an increased risk of coronary artery disease in codominant model (OR = 1.96, 95 % CI, 1.12-3.42; RR 1.35(1.05-1.75, p=0.017) of microRNA-423CA genotype and significant association in dominant model (OR 1.97, 95% CI (1.14-3.39), (CA+AA vs CC) and non-significant association for recessive model (OR=1.42, 95%CI=0.42-4.83, P=0.56, AA vs CC+CA).While, the A allele significantly increased the risk of coronary artery disease (OR =1.56, 95 % CI, 1.03-2.37; p=0.035) compared to C allele. Therefore, it was observed that more than 1.96, 1.97 and 1.56 fold increased risk of developing coronary artery disease. Conclusion: Our findings indicated that microRNA-423 CA genotype and A allele are associated with an increased susceptibility to Coronary artery disease.

Potential Impact of MicroRNA Gene Polymorphisms in the Pathogenesis of Diabetes and Atherosclerotic Cardiovascular Disease

“…The SNPs can also be the cause of variation in drug response between individuals [21]. Moreover, they can be the cause of several pathophysiological disorders such as diabetes [22][23][24][25] cancers or atherosclerosis [21,[26][27][28][29][30][31], obesity, hypertension, psychiatric disorders [20], inflammatory and autoimmune diseases [32]. SNPs at the miRNA gene may enhance, reduce expression, change maturation of miRNA, or disrupt miRNA-mRNA binding [33].…”

“…Disruption of miRNA-mRNA binding may contribute to the development of different types of human diseases. This disruption may result from gene polymorphism at the miRNA target site [34][35][36], or polymorphism in miRNA genes [27,29,30,[37][38][39][40][41].…”

The rs6505162 C>A polymorphism in themiRNA-423gene exhibits a protective element of coronary artery in a southern Chinese population with Kawasaki disease

“…(29–31) Other finding hinted that miRNA-423 A allele and CA genotypes could enhance the risk of coronary artery disease(CAD). (25) Hakimzadeh reported that up-regulation of miR423-5p could identify the sick with low coronary collateral volume. (32) Alterations in the expression extent of 8 miRNAs including miRNA-423 participating in the immune pathway might be involved in the immune process in the early stages of diabetes, through the alterations of the four cytokines IL-4., IL-10, IL-21, IL-22 and three pancreatic autoantibodies IA-2A, ICA, GAD65A.…”

“…(19–23) Colorectal carcinoma whose potential biomarker might be miR-423 rs6505162 has been studied by Jia, W.(24) Jha, Chandan K detected that The gene mutation in microRNA-423 was in connection with enhancive susceptibility to CHD. (25)The miRNA-423 rs6505162 having a certain relationship with CHD in prognosis, as studied in this article, is associated with HDL. (26) However, the connection of the miRNA-423 rs6505162 C>A polymorphism with KD susceptibility has not been investigated so far.…”

Diagnostic and theranostic microRNAs in the pathogenesis of atherosclerosis

“…Thus, the combination of miR‐92a overexpression and elevated systolic blood pressure may be helpful in predicting the risk of acute coronary syndrome. Moreover, Jha et al carried out research on miR‐423 gene variability and found that miR‐423 CA genotype was associated with an elevated susceptibility to CAD.…”