In The Early Diagnosis of Coronary Artery Disease at Adıyaman Province, The Long Non-coding RNAs in the Blood (MEG3, MALAT1, MIAT, MCM3AP-AS1): Could It Be Early Biomarkers?

Coronary artery disease (CAD), which is the most common form of heart disease and which develops on the basis of atherosclerosis, ranks first among the causes of death in our country and in the whole world. Along with traditional and newly defined risk factors, genetic based reasons also play a very important role in CAD aetiology. Environmental factors and several pathways with a large number of genes play a role in the pathophysiology of CAD, which is a polygenic disease. It has been shown that epigenetic factors contribute to CAD development and long noncoding RNAs (lncRNA), which are important epigenetic regulators, play a role in disease development. lncRNAs have begun to be researched as a new biomarker and treatment target for the diagnosis and prognosis of cardiovascular diseases, especially CAD, due to their stability in plasma and other body fluids. In our study, lncRNA expression levels were measured from peripheral whole blood samples of cases that underwent coronary angiography for diagnostic or therapeutic purposes with a suspicion of CAD. For this purpose, a total of 90 cases, 45 cases whose coronary angiographies were normal (<%50 constriction, non-obstructive) and 45 cases who were diagnosed with CAD after critical constriction (>%50 constriction, obstructive) was found in their coronary arteries, were included in study. lncRNA expression levels were researched by quantitative real-time polymerase chain reaction (qRT-PCR) method for MEG3, MALAT1, MIAT and MCM3AP-AS1 after total RNA acquisition and cDNA conversion from peripheral whole blood samples. qRT-PCR results were analyzed statistically by using 2-ΔCt formula. Mann Whitney U test was used to compare lncRNA expression levels and χ 2 (Chi-square) test was used in the statistical assessment of lncRNA expression relationship according to demographic characteristics and clinical findings. Statistically significant expression differences were found between groups for MEG3 and MIAT, which are among the four candidate lncRNA researched (p<0.02 and p<0.0003). In addition, statistically significant expression differences were found in patients who did not have DM, HT, family history and male patients as a result of MEG3 expression studies. Statistically significant expression differences were also found in patients who did not have DM and those who had HT history and male patients as a result of MIAT expression studies. It is known that lncRNAs which are detected expression differences target to genes which have specific roles in atherosclerosis and angiogenesis (VEGFR2 and NLRP3 gene for MEG3, VEGF for MIAT) in experimental studies. We believe that these lncRNAs, which were detected different expression levels in patient groups, contributed to the development of disease by having a role in CAD pathogenesis and they may be a biomarker candidate for this disease and a possible treatment target. It is thought that the results of the study will contribute to the management of CAD cases and especially to mechanisms related with atherosclerosis and angiogenesis with a different perspective. Keywords: Coronary artery disease, lncRNA, atherosclerosis, angiogenesis, MEG3, MIAT