The Role of Polymorphism in the Endothelial Homeostasis and Vitamin D Metabolism Genes in the Severity of Coronary Artery Disease

Abstract

Coronary artery disease (CAD) remains one of the leading causes of cardiovascular morbidity and mortality worldwide. The maintenance of endothelial homeostasis and vitamin D metabolism play an important role in CAD pathogenesis. This study aimed to determine the association of endothelial homeostasis and vitamin D metabolism gene polymorphism with CAD severity. A total of 224 low-risk patients (SYNTAX score ≤ 31) and 36 high-risk patients (SYNTAX score > 31) were recruited for this study. The serum level of E-, L- and P-selectins; endothelin; eNOS; 25OH; and 1.25-dihydroxy vitamin D was measured using an enzyme-linked immunosorbent assay (ELISA). Polymorphic variants in SELE, SELP, SELPLG, END1, NOS3, VDR and GC were analyzed using a polymerase chain reaction (PCR). We found no differences in the serum levels of the studied markers between high- and low-risk patients. Three polymorphic variants associated with CAD severity were discovered: END1 rs3087459, END1 rs5370 and GC rs2298849 in the log-additive model. Moreover, we discovered a significantly decreased serum level of 1.25-dihydroxy vitamin D in high-risk CAD patients with the A/A-A/G genotypes of the rs2228570 polymorphism of the VDR gene, the A/A genotype of the rs7041 polymorphism of the GC gene and the A/A genotype of the rs2298849 polymorphism of the GC gene.

Keywords: ELISA; SYNTAX; cardiovascular diseases; coronary artery disease; endothelial homeostasis; genetic polymorphism; vitamin D.