Why the study?
Genetic causes and mechanisms for CAD remain largely unclear, and dysregulated expression of TBX5, a cardiac developmental regulator, may be involved.
Are genetic variants in the TBX5 gene promoter associated with acute myocardial infarction and altered promoter activity?
Are genetic variants in the TBX5 gene promoter associated with acute myocardial infarction and altered promoter activity?
Novel genetic variants in the TBX5 gene promoter may alter its activity and contribute to the development of acute myocardial infarction as a rare risk factor.
TBX5 promoter variants may confer rare AMI risk in select patients; leaves open replication in larger cohorts before any screening role.
BACKGROUND: Coronary artery disease (CAD), including acute myocardial infarction (AMI), is a common complex disease. Although a great number of genetic loci and variants for CAD have been identified, genetic causes and underlying mechanisms remain largely unclear. Epidemiological studies have revealed that CAD incidence is strikingly higher in patients with congenital heart disease than that in normal population. T-box transcription factors play critical roles in embryonic development. In particular, TBX5 as a dosage-sensitive regulator is required for cardiac development and function. Thus, dysregulated TBX5 gene expression may be involved in CAD development. METHODS: TBX5 gene promoter was genetically and functionally analysed in large groups of AMI patients (n = 432) and ethnic-matched healthy controls (n = 448). RESULTS: Six novel heterozygous DNA sequence variants (DSVs) in the TBX5 gene promoter (g.4100A > G, g.4194G > A, g.4260 T > C, g.4367C > A, g.4581A > G and g.5004G > T) were found in AMI patients, but in none of controls. These DSVs significantly changed the activity of TBX5 gene promoter in cultured cells (P < 0.05). Furthermore, three of the DSVs (g.4100A > G, g.4260 T > C and g.4581A > G) evidently modified the binding sites of unknown transcription factors. CONCLUSIONS: The DSVs identified in AMI patients may alter TBX5 gene promoter activity and change TBX5 level, contributing to AMI development as a rare risk factor.
No takes yet. Share an insight, caveat, or question.
Wang et al. (2019) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: