TFAM Expression, rs1937 Variant, and Mitochondrial DNA Copy Number in Egyptian Myocardial Infarction Patients

Myocardial infarction (MI) is a fatal condition that causes damage to the heart muscle by abruptly stopping blood flow and oxygenation. Mitochondrial transcription factor A (TFAM) and mitochondrial DNA copy number (mtDNA CN) show an increased rate of association with development of several human diseases and malignancies. This paper, therefore, aims to identify the possible relation among mtDNA CN and its regulating gene TFAM (expression of the gene and rs1937 polymorphism) as markers in myocardial infarction among Egyptians. A total of 200 participants were enrolled and divided into two groups. Group 1 included 100 myocardial infarction patients with ST-segment elevation (STEMI) recruited from from the Coronary Care Unit (CCU) of Menoufia University Hospitals, while group 2 included 100 Controls. Blood samples were collected from all participants immediately after diagnosis of MI and before beginning therapy. TFAM SNP (rs1937) was determined by the allelic discrimination TaqMan technique, and mtDNA CN and TFAM gene expression were detected using real-time quantitative PCR in 100 MI patients and 100 controls. TFAM mRNA expression and mtDNA copy number were profoundly reduced in MI patients than controls. Analysis of genotype showed that the TFAM rs1937 variant distribution was in Hardy-Weinberg equilibrium. The C allele and the GC genotype were substantially more frequent in the patients’ cohort (p = 0.006 and 0.005, respectively). The GC genotype of the TFAM polymorphism (rs1937) showed a preliminary association with MI in STEMI patients. Limitations of this study are the absence of longitudinal pre-MI or post-recovery data. TFAM mRNA expression and mtDNA copy number were measured in whole blood without adjustment for leukocyte subpopulations or platelet counts. Small number of C carriers of TFAM rs1937 variant and absence of CC genotype limited statistical power and requires replication in larger Egyptian cohort. These findings suggest that decreased TFAM gene expression and mtDNA CN were significant biomarkers associated with acute myocardial infarction in STEMI patients.