Association Between Genotype and Plasma Levels of EPCR in Type 2 Diabetes Mellitus in Jazan Region, Saudi Arabia: A Case-Control Study

Background: Type 2 diabetes mellitus (T2DM) is a major health burden in Saudi Arabia. Its prevalence is estimated at 16.4% to 28% among adults. It is characterized by chronic hyperglycemia inducing low-grade inflammation, which drives various physiological changes, including endothelial dysfunction. The endothelial protein C receptor (EPCR) is a membrane-bound receptor expressed on normal endothelial cells and is released upon endothelial dysfunction into the blood as soluble EPCR (sEPCR). Increased cleavage and release of EPCR is associated with the EPCR rs867186 polymorphism. Therefore, the current study aimed to investigate the pattern and frequency of EPCR rs867186 polymorphism and plasma levels of sEPCR in patients with T2DM and healthy controls. Materials and Methods: The current case-control study was performed in Jazan region, Saudi Arabia. Two hundred and thirty-four blood samples were collected from the 136 patients with T2DM and 98 healthy controls for DNA analysis and hematological and biochemical assessments. Results: The plasma levels of sEPCR were significantly elevated in T2DM patients compared to controls, despite no association being found between sEPCR levels and the genotype in either cohort. The pattern of EPCR rs867186 polymorphism revealed AA in 83.8% (n=196) and AG in 16.2% (n=38) of total cohorts (n=234), with comparable genotype distribution between patients and controls. Conclusion: This study highlights a significant elevation in plasma levels of sEPCR in patients with T2DM, indicating increased shedding of membrane EPCR and suggesting endothelial dysfunction. Importantly, the levels of sEPCR were not associated with rs867186 polymorphism. These findings suggest that sEPCR could be a useful biomarker for predicting early inflammation and endothelial dysfunction in T2DM. Keywords: EPCR, polymorphism, soluble EPCR, type 2 diabetes mellitus