Chitotriosidase Enzyme Activity and miRNA-146a expression and their value as potential Biomarkers of subclinical Atherosclerosis in type 2 Diabetes Mellitus

Abstract

Background: Type 2 diabetes T2DM is a common disease with increased mortality and morbidity due to vascular complications. Carotid Intimal-Medial Thickness (CIMT) is being used as a marker to assess subclinical atherosclerosis.MicroRNA (miR-146a) is a new discoveredbiomarker that regulates endothelial cell function and vascular inflammation, together with Chitotriosidase (CHIT1)enzyme being involved mainly in the immune and inflammatory responses.This study aimed to investigate an assumed association between CHIT1 activity and miR-146a gene expression in type 2 diabetes patients for detection of endothelial dysfunction and subclinical atherosclerosis, in association with CIMT.Material and Methods: 30 control subjects (group I) and 100 patients diagnosed as T2DMclassified according to CIMT results; group II (38 patient) with CIMT value less than 0.7mm and group III (62patients) with CIMT value more than 0.7mm. Plasma CHIT1 activity was measured fluorometricallyand quantitative Real Time PCR (qPCR) for miR-146a. Routine laboratory parameters such as blood glucose, lipid profile, glycated hemoglobin were also measured.Results: revealedCHIT1activity was significant high(p < 0.001) in group II and III diabetic patients compared to group I, also it waspositively correlated with CIMT and other parameters as glycemic control, lipid profile, duration of disease and blood pressure. On the other hand, plasma miR-146a was significantly reduced (p < 0.001) in group III and was negatively correlated with CIMT and other parameters. Conclusion:IncreasedCHIT1activity may be due to the associated changes in the relative gene expression of miRNA 146a in patients with increased CIMT above 1mm. Moreover, evaluation of microRNA 146a gene expression can be used as useful biomarker for detection of endothelial dysfunction and development of atherosclerosis in T2DM.