Abstract 10604: Rs11091046-a Increases the Expression of Angiotensin Ii Receptor 2 Gene by Mir-208a

Abstract

Introduction: Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. The mechanism of AF still remains unknown. In case - control study, we found that rs11091046 located in 3' - UTR of angiotensin II receptor 2 (AGTR2) gene was related to non - familial AF in Chinese Han population. It is necessary to figure out the mechanism of rs11091046 in non - familial AF. Methods: We predicted cohesion change between rs11091046 and miR-208a by RNAhybrid software and confirmed the prediction of cohesion change between rs11091046 and miR-208a by double luciferase reporter system. We detected the expression of AGTR2 gene in right atrium of patients with AF and subjects with sinus rhythm by quantitative real-time PCR. Results: RNAhybrid software showed that the cohesion between 3' - UTR of AGTR2 gene and seed region of miR - 208a was reduced because of the polymorphism of rs11091046 (wide type C mfe: -16.4kcal/mol, mutant type A mfe: -13.7kcal/mol). We also observed that the luciferase activity of transfected cells with miR - 208a and wild - type rs11091046 - C was significantly decreased by 59% while it was relatively enhanced by 22% with miR - 208a and mutant - type rs11091046 - A (Figure 1 up panel). The mRNA level of AGTR2 gene in right atrium of patients with AF was significantly increased compared with subjects with sinus rhythm. The mRNA level of AGTR2 gene in cardiomyocyte transfected by miR - 208a mimic was higher than cardiomyocyte transfected by miR - 208a (Figure 1 down panel). Conclusion: The polymorphism of rs11091046 in AGTR2 gene reduced the cohesion between 3 '- UTR of AGTR2 gene and seed region of miR - 208a, which increased the expression level of AGTR2 gene leading to occurrence of AF. Figure 1 Up panel The relative luciferase activity of transfected cells with wild - type rs11091046 - C and mutant - type rs11091046 - A (BK389: pmirGLO - rs11091046 - C, BK390: pmirGLO - rs11091046 - A). ** P < 0.01. Down panel The mRNA level of AGTR2 gene in cardiomyocyte transfected by miR - 208a mimic and miR - 208a. * P < 0.05.