Association of Endothelin-1 (EDN1) rs5370 polymorphism and serum ET-1 levels with coronary artery disease and hypertension in Duhok Province population

Abstract Background Coronary artery disease (CAD) and hypertension are major cardiovascular diseases (CVDs) influenced by both environmental and genetic factors. Endothelin-1 (ET-1), a potent vasoconstrictor encoded by the EDN1 gene, is involved in vascular regulation. The rs5370 (G + 691 T, Lys198Asn) polymorphism has been associated with CVD susceptibility, though findings differ by population. This study assessed the association between EDN1 rs5370 polymorphism, serum ET-1 levels, and CVD risk in the Duhok population. Methods A case–control study included 202 individuals (> 35 years) divided into four groups: controls, CAD-only, hypertension-only, and combined CAD-hypertension. Genomic DNA was genotyped using allele-specific PCR. Serum ET-1 was measured using ELISA. Statistical analyses included Chi-square, ANOVA, Pearson correlation, and ROC curve analysis. Results The TT genotype was significantly more prevalent in CAD (28.0%) and CAD + hypertension (21.3%) groups compared to controls (6.7%) ( P = 0.0002 and 0.0183, respectively). No significant differences were found in the hypertension-only group. Serum ET-1 levels were highest in the CAD + hypertension group. A strong positive correlation was found between TT genotype and ET-1 levels ( r = 0.7310). ROC analysis identified systolic pressure (AUC = 0.787) and age (AUC = 0.782) as key diagnostic markers. Conclusion The EDN1 rs5370 TT genotype is significantly associated with increased CAD and combined CVD risk in the Duhok population. While group differences in ET-1 levels were evident, genotype-dependent differences were only seen through correlation analysis. The rs5370 polymorphism may serve as a genetic marker for CAD susceptibility.