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

Area of Science:

• Cardiovascular Genetics
• Molecular Cardiology

Background:

• Coronary artery disease (CAD), including acute myocardial infarction (AMI), is a complex genetic disorder with largely unknown causes.
• A higher incidence of CAD in individuals with congenital heart disease suggests a role for cardiac developmental genes.

Purpose of the Study:

• To investigate the role of GATA binding protein 4 (GATA4) gene promoter variants in the development of AMI.
• To analyze GATA4 gene promoter activity in patients with AMI compared to healthy controls.

Main Methods:

• Analysis of the GATA4 gene promoter in 395 AMI patients and 397 healthy controls.
• Identification and characterization of DNA variants, including single-nucleotide polymorphisms.
• Electrophoretic mobility shift assay to assess transcription factor binding.

Main Results:

• Fourteen DNA variants were identified in the GATA4 promoter region.
• Three novel heterozygous variants (g.31806C>T, g.31900G>C, g.32241C>T) were found in three AMI patients.
• These variants significantly increased GATA4 gene promoter activity, and g.32241C>T affected transcription factor binding.

Conclusions:

• Novel DNA variants in the GATA4 gene promoter may contribute to AMI development.
• Altered GATA4 promoter activity and subsequent changes in GATA4 levels are implicated in AMI pathogenesis.