PSMA6 Polymorphism, DKK1, and OPG in Coronary Artery Disease: Evidence from a Case–Control Study.

Background: Coronary artery disease (CAD) remains a leading global health problem. Genetic biochemical markers such as PSMA6 rs1048990, osteoprotegerin (OPG), Dickkopf-1 (DKK1) may provide novel insights into CAD pathogenesis. This study aimed to explore the association of serum OPG, Dkk-1 levels, PSMA6 rs1048990 (-8C>G) gene genetic variation with CHD. Methods: This case–control study included 72 angiographically confirmed CAD patients 72 age-sex-matched controls. Fasting glucose lipid profiles were measured. Serum OPG (pmol/L) DKK1 (pg/mL) were quantified by ELISA, PSMA6 rs1048990 genotypes were determined using real-time PCR with melting-curve analysis. Results: The CG ,GG genotypes, as well as the G allele, were significantly more frequent among cases (CG+GG vs CC, p = 0.030; G vs C, p = 0.008). OPG levels were higher in patients (6.26 ± 1.83 vs 3.96 ± 0.74 pmol/L; p < 0.001), while DKK1 levels showed no significant difference between cases and controls (4.84 ± 1.27 vs 4.59 ± 1.19 pg/mL; p = 0.292). After adjustment for confounders, the associations between OPG, PSMA6 G allele, CAD remained significant (p < 0.05). OPG showed strong diagnostic performance (AUC = 0.862; cut-off >5.2 pmol/L; sensitivity 79.2%, specificity 97.2%), whereas DKK1 was not predictive (AUC = 0.553; p = 0.271). Conclusions: This case–control study on an Egyptian cohort identified a significant association between the PSMA6 rs1048990 polymorphism elevated serum OPG levels with increased CHD risk. The G allele of PSMA6 may enhance disease susceptibility via inflammatory proteasomal pathways, while OPG demonstrated strong diagnostic performance, highlighting its potential as a predictive biomarker.