Association of cathepsin D (CTSD) polymorphism and serum levels with myocardial infarction risk in type-2 diabetes mellitus

Background & objective: Type 2 diabetes mellitus (T2DM) significantly increases the risk of cardiovascular disease, including myocardial infarction (MI). Cathepsin D (CTSD), which is involved in the metabolic and inflammatory pathways, may serve as a diagnostic biomarker. This study investigated the association between the CTSD polymorphism (rs928508030) and MI in patients with T2DM, and evaluated CTSD, adiponectin, and TNF-α as diagnostic biomarkers. Methodology: This cross-sectional study enrolled 120 participants: 40 controls, 40 T2DM patients, and 40 T2DM patients with MI. The serum levels of CTSD, adiponectin, and TNF-α were measured using ELISA. Genotyping of CTSD rs928508030 SNP was performed using tetra-ARMS PCR. Statistical analyses included ANOVA, chi-square tests, ROC curve analysis, and Pearson correlations. Results: T2DM and MI patients exhibited significantly higher CTSD (374 ± 118 ng/L) and TNF-α (160 ± 52.8 ng/L) and lower adiponectin (9.0 ± 1.7 mg/L) levels than the controls (P < 0.001). The A allele of rs928508030 was enriched in the T2DM (54%) and T2DM and MI (51%) groups compared to the controls (0%, P < 0.001). ROC analysis demonstrated high diagnostic accuracy for CTSD (AUC = 94%), adiponectin (AUC = 93%), and TNF-α (AUC = 93%) in MI detection. Positive correlations were found between CTSD and TNF-α (r = 0.514) and HbA1c (r = 0.554), whereas adiponectin was inversely correlated with metabolic inflammatory markers (P < 0.05). Conclusion: CTSD rs928508030 A allele and elevated CTSD levels were associated with increased MI risk in T2DM patients. CTSD, along with adiponectin and TNF-α, exhibits strong diagnostic potential for MI in this population. These findings underscore the role of the genetic and inflammatory pathways in diabetic cardiovascular complications. Abbreviations: CTSD: Cathepsin D, DM: diabetes mellitus, EDTA: ethylenediaminetetraacetic acid, T2DM: Type 2 diabetes mellitus, MI: myocardial infarction, SNP: single nucleotide polymorphisms, TNF-α: Tumor necrosis factor-alpha Keywords: Cathepsin D; Cardiovascular Complications; Diabetes Mellitus; Myocardial Infarction; T2DM; TNF-α; Adiponectin. Citation: Hassan MH, Jabir FA. Association of cathepsin D (CTSD) polymorphism and serum levels with myocardial infarction risk in type-2 diabetes mellitus. Anaesth. pain intensive care 2025;29(8):980-987. DOI: 10.35975/apic.v29i8.3027 Received: May 09, 2025; Revised: October 26, 2025; Accepted: January 01, 2025