PURPOSE: Apelin is a secreted peptide hormone involved in vasodilation, fluid homeostasis, and angiogenesis, and is therefore considered an important regulator of cardiovascular physiology. The APLN T-1860C (rs56204867) polymorphism is a genetic variation in the promoter region of the apelin gene (APLN) that is associated with increased susceptibility to cardiovascular risk factors. This study aimed to elucidate the relationship between the apelin gene -1860T>C single-nucleotide polymorphism, plasma apelin levels, and the risk of coronary artery disease (CAD) in a Syrian population. PATIENTS AND METHODS: A case-control study was conducted, comprising 108 CAD patients and 114 healthy controls. Plasma apelin levels were quantified using an enzyme-linked immunosorbent assay (ELISA). The apelin -1860T>C gene polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Our findings reveal that mean plasma apelin levels were significantly lower in CAD patients (2737.81 ± 1205.01 pg/mL) compared to controls (4258.73 ± 2119.12 pg/mL; p < 0.001). Notably, these levels did not correlate with any of the other anthropometric parameters studied. In females, the frequencies of the TC genotype (30.5% vs 10.5%, p = 0.041, odds ratio [OR] = 3.75) and the mutant C allele (15.2% vs 5.2%, p = 0.043, OR = 3.256) were significantly higher in CAD patients than in controls. Whereas no significant differences were observed in male subjects. Although the plasma apelin level was lower in patients and controls with the TC genotype, this difference was not statistically significant (p > 0.05). CONCLUSION: Our findings indicate that the APLN -1860T>C polymorphism is associated with a higher risk of CAD in the Syrian population, particularly among females, suggesting a sex-specific genetic predisposition. Furthermore, reduced plasma apelin levels in patients suggest that apelin may play an independent role in the development of CAD, warranting further exploration.