Genetic Basis of Atherosclerosis: The Role of PLAU Gene Polymorphism in Coronary Artery Disease

Abstract

Background:

Coronary artery disease (CAD) is a multifactorial disorder influenced by both environmental and genetic factors. The PLAU gene, which plays a key role in fibrinolysis, inflammation, and extracellular matrix remodeling, has been implicated in atherosclerotic plaque progression. However, the relationship between PLAU polymorphisms and different clinical manifestations of CAD remains insufficiently clarified.

Aims:

This study aimed to investigate the distribution of the PLAU rs2227564 polymorphism in patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS), and angiographically normal controls, and to evaluate its potential association with CAD susceptibility.

Methods:

A total of 196 participants (ACS: 66, CCS: 65, controls: 65) who underwent coronary angiography were prospectively enrolled. Genotyping of the PLAU rs2227564 polymorphism was performed using real-time polymerase chain reaction with the TaqMan SNP Genotyping Assay. Genotype and allele frequencies were compared among groups. Dominant, recessive, and allelic genetic models were analyzed, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

Results:

Overall genotype and allele distributions were similar across the study groups (p = 0.737). However, under the dominant genetic model (CT + TT vs. CC), carriers of at least one T allele showed significantly increased susceptibility to both ACS (OR: 6.84, 95% CI: 1.47–31.89, p = 0.009) and CCS (OR: 6.60, 95% CI: 1.43–30.48, p = 0.008) compared with controls. No significant associations were observed in the recessive or allelic models.

Conclusion:

Although the rs2227564 polymorphism was not independently associated with CAD based on the overall genotype distribution, the dominant model findings suggest that carrying at least one T allele may contribute to disease susceptibility in specific clinical and population contexts. These findings should be considered hypothesis-generating and require confirmation in larger multicenter studies with functional validation.