Mitochondrial Mutations in tRNAGlu and Cytochrome b Genes Associated with Iranian Congenial Heart Disease

Distribution of mitochondrial oxidative energy metabolism is a characteristic of cardiomyocyte dysfunction and congenital familial and sporadic heart diseases. Several studies have indicated that mutations in mitochondrial DNA, particularly in tRNAs and MT-CYB coding for cytochrome B in complex III (CIII), were associated with cardiologic disorders. We hypothesized that mutations in these positions might play an important causal or modifying role in congenital heart defects. Congenital Heart Diseases (CHDs) are the most common anomaly in newborns and the leading non-infectious cause of mortality in the first year of life. These defects are multifactorial complex diseases resulting from both genetic predisposition and environmental risk factors. Despite advances in molecular medicine, the genetic mechanism underlying mitochondrial genetic determinants of development of CHD has remained poorly understood.
The present study aimed to identify the association between mitochondrial mutations in tRNAGlu and Cytb genes and CHD in Iranian patients.
In this case-control study, tRNAGlu and MT-CYB genes were analyzed in DNA isolated from peripheral blood of 84 Iranian pediatric patients with non-familial CHD and 72 controls for alterations. The cases and healthy controls were matched regarding age and gender.
A total of three nucleotide variations were detected by Polymerase Chain Reaction-Single-Strand Conformation Polymorphism (PCR-SSCP) and sequencing. One of them was located in tRNAGlu (A14696T) found in a child with tetralogy of fallot and ventricular septal defect, which was assessed as a pathogen mutation. The second mutation was a homoplasmic variant (m.14766C > T) in cytb gene and was not detected in the healthy controls.This variant altered an amino acid (T7I) with moderately interspecific amino acid conservation indicative of the functional importance of the residue. Finally, a homoplasmic synonymous variation (T14783C) was observed in 70.4% of the CHD patients.
The results suggested that mitochondrial mutations might be associated with CHD in Iranian pediatric patients. Thus, more patients with CHD should be examined for mutations in mtDNA in order to clarify the role of variants.