Functional genetic variants of the GATA4 gene promoter in acute myocardial infarction

: Coronary artery disease (CAD), including acute myocardial infarction (AMI), is a common complex disease; however, the genetic causes remain largely unknown. Recent epidemiological investigations indicated that the incidence of CAD in patients with congenital heart diseases is markedly higher than that observed in healthy controls. It was therefore hypothesized that the dysregulated expression of cardiac developmental genes may be involved in CAD development. GATA binding protein 4 (GATA4) serves essential roles in heart development and coronary vessel formation. In the present study, the GATA4 gene promoter was analyzed in patients with AMI (n=395) and in ethnically‑matched healthy controls (n=397). A total of 14 DNA variants were identified, including two single‑nucleotide polymorphisms. Three novel heterozygous DNA variants (g.31806C>T, g.31900G>C and g.32241C>T) were reported in three patients with AMI. These DNA variants significantly increased the activity of the GATA4 gene promoter. The electrophoretic mobility shift assay revealed that the DNA variant g.32241C>T influenced the binding ability of transcription factors. Taken together, the DNA variants may alter GATA4 gene promoter activity and affect GATA4 levels, thus contributing to AMI development.