Hypomethylation and decreased expression of BRG1 in the myocardium of patients with congenital heart disease

BackgroundBRG1, an ATPase subunit of the SWItch/Sucrose Non-Fermentable complex, is tightly associated with cardiac development. However, little is known about the association between the pathogenesis of CHD and BRG1. MethodsThe methylation of a BRG1 promoter and a novel CpG island in the second intron was analyzed in the myocardium of congenital heart disease (CHD) patients (n=24) and normal controls (n=11) using pyrosequencing and the MassARRAY platform. BRG1 expression was sketched in the normal fetal and postnatal heart using real-time PCR. BRG1 mRNA and protein expression was detected by means of real-time PCR and immunohistochemistry. The expression of GATA4 was analyzed with real-time PCR. ResultsThe CpG shore in the second intron of BRG1 was hypomethylated in the myocardium of patients (p<0.05). BRG1 showed a high level of expression in the normal fetal heart in the second trimester (p<0.01). Compared with that of the normal subjects, BRG1 expression was decreased by 70% in the myocardium of patients (n=92; p<0.05). Of note, the expression of GATA4 was significantly correlated with BRG1 expression (r=0.7475; p=0.0082) in the myocardium, and it was also decreased by 70% in these patients (n=92; p<0.05). ConclusionThese results suggested that the early high expression of BRG1 in fetal hearts maintained normal cardiac development and that the abnormal hypomethylation and decreased expression of BRG1 in human hearts probably affect the expression of GATA4, which affects the pathogenesis of CHD. Birth Defects Research 109:1183-1195, 2017. (c) 2017 Wiley Periodicals, Inc.