Abstract Background: Coronary artery disease (CAD) remains a leading cause of mortality in patients with type 2 diabetes (T2DM). Both conditions share genetic and environmental etiologies, making T2DM a unique risk factor for CAD. Despite advancements, no highly accurate genetic or clinical prediction models exist to identify patients at high risk for complex coronary disease. Methods: A cross-sectional genetic epidemiology study was conducted at a cardiovascular center in Manizales, Colombia, involving 106 T2DM patients with documented coronary heart disease (CHD). Genetic analysis focused on 11 single nucleotide polymorphisms (SNPs) using polymerase chain reaction (PCR) and TaqMan assays. Clinical and genetic data were analyzed to assess associations with CAD complexity, defined as monovascular (one vessel) or polyvascular (≥2 vessels) involvement. Statistical methods included bivariate analyses, binary logistic regression, and Bonferroni correction for significance. Results: Among participants (mean age 68.1 ± 8.3 years; 53.7% male), 33 had monovascular disease, and 73 had polyvascular disease. Male sex (p = 0.016) and a significant genetic profile (PRP-5: rs1412830-CDKN2A/B, rs2074192-ACE2, rs4420638-APOE, rs646776-CELSR2, rs7903146-TCF7L2) were associated with polyvascular disease. PRP-5 demonstrated an odds ratio (OR) of 5.2 (p = 0.007) for complex CAD. Other metabolic and clinical parameters showed no significant differences between genetic risk groups. Conclusions: This study identifies a polygenic risk profile (PRP-5) associated with complex CAD in T2DM patients, independent of traditional clinical factors. These findings support the hypothesis of genetic contributions to CAD severity and suggest the need for longitudinal studies to evaluate this risk profile's clinical utility. As the first cohort-based genetic study in Hispanoamerica, it highlights the high prevalence of relevant alleles in this population and provides a foundation for future research into personalized cardiovascular risk stratification.

The authors have declared no competing interest.

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