Mitochondrial TRNA Mutations And Epidemiological Study In Patients With Acute Myocardial Infarction

Background:Myocardial infarction,as a globally lethal disease,has been the focus of clinical and basic research.The occurrence and development of myocardial infarction are affected by the patient’s own genes and various factors.Mitochondria are indispensable organelles in eukaryotic cells.They possess a variety of biological functions including the production of ATP,and the heart relies on the energy produced by mitochondria to achieve pump function.However,at present,the focus of gene research on myocardial infarction is still on nuclear genes,and the relationship between mitochondrial genes and MI is still lacking.Methods:Blood samples were collected from 1000 patients with myocardial infarction in 18 hospitals in Zhejiang Province.Whole blood DNA were extracted,PCR and sequencing were did for each DNA sample.Species conservation,population conservation,and structural functional analysis were performed on the obtained mutation sites.The clinical data of patients with myocardial infarction were collected and analyzed,and the effects of mitochondrial tRNA mutations on clinical symptoms were also analyzed.Results:(1)After sequencing and analyzing,total 792 patients’ mitochondrial tRNA data were finally obtained,and 136 mutation sites were found in 415 patients.Among these 136 mutation sites,49 sites’ conservation rate was>85%(distributed in 106 patients),and 27 sites’ conservation rate was>95%(distributed in 51 patients).The proportion of all mutation sites in the normal population was less than 3%.Some mutations have been reported may be associated with Leber hereditary optic neuropathy(LHON),neonatal encephalopathy,deafness,hypertension,dilated cardiomyopathy and other diseases.(2)Among those 652 patients with full clinical data,104 mutation sites were found.According to the screening criteria,37 suspicious mutation sites were finally obtained.(3)16-26 pedigrees(carrying the T10003C mutation)and 11-5 pedigrees(carrying the A14693G mutation)were found.Both pedigrees are typical maternal inherited myocardial infarction.At the same time,the mutations T10003C and A14693G have not been reported to be associated with myocardial infarction.(4)The patients were classified into two groups according to whether they carrying the suspicious mutation sites,and their clinical manifestations were studied.LVEF was significantly lower in patients with suspicious mutations than in patients without(54.5 vs 56%,p=0.023).In addition,the TNI carrying suspicious mutations was slightly higher than those without(10.28 vs 6.1 ng/ml,p=0.066),and the Gensini score of patients carrying suspicious mutations was slightly higher than patients who without mutation sites(72 vs 54,p= 0.072).Although there was no significant difference,patients with suspicious mutations had the trends of higher troponin and more severe coronary stenosis.There was no significant difference in baseline levels,blood lipid levels,blood routine,CK,CKMB,BNP,ProBNP,length of hospital stay,etc.between the two groups.Conclusions:In this study,multiple suspicious myocardial infarction-related mitochondrial tRNA mutation sites were found in Chinese patients with myocardial infarction.At the same time,clinical studies have shown that carrying these suspicious mutations can cause patients with reduced heart function,which in turn makes the patient’s condition worsened.