The study of mitochondrial ATP6, ND3 and COX3 gene nucleotide variations in Iranian patients with atherosclerosis by PCR-SSCP

Atherosclerosis is a complex arterial disease that is caused due to the interaction of genetic and environmental factors. Mutations in the mitochondrial genome have probably a direct effect on increased oxidative stress and thereby cause progression of the disease. The aim of the current study was to identify the possible nucleotide changes in the mitochondrial ATP6, ND3 and COX3 genes in Iranian patients with atherosclerosis.
In this case-control study, DNA was extracted from peripheral blood of 90 patients with atherosclerosis and 95 healthy individuals by standard method. The regions of the mitochondrial genome including ATP6, ND3 and COX3 genes were studied by PCR-SSCP; and banding shift specimens were sequenced to determine the exact nucleotide changes. The obtained data were analyzed using the Fisher's exact test and GraphPad prism software.
The results of SSCP and DNA sequencing lead to the detection of three nucleotide changes in ATP6 gene including a synonymous polymorphism at position m.9034 G>A, and an SNP at position m.9055 G>A, in which alanine is converted to tyrosine and synonymous hetroplasmic variant at m. 9162C>T. Also, it was found three homoplasmic nucleotide variations including synonymous m.9602A>G, m.9899T>C related to histidine amino acid and homoplasmic variant m.9929C>A that resulted in changing of tyrosine to stop codon.
. Since it has been proven, m.9055G>A variant increases the risk of developing breast cancer, and on the other hand, this polymorphism has also been reported in the Caucasian population of Parkinsons; Therefore, it can be said that the combination of this mutation with other predisposing factors increases the severity of coronary heart disease. Investigating other mitochondrial genes could be regarded important in order to find the the relationship between nucleotide changes of mitochondrial genes cardiovascular diseases.