The G allele and GG Genotype of the Junctional Cadherin 5 Associated (JCAD) Is a Biomarker Predicting Myocardial Infarction in Slovenian Subjects with Type 2 Diabetes Mellitus

Background: Patients with type 2 diabetes mellitus (T2DM) have a two- to fourfold higher risk of myocardial infarction (MI), yet genetic determinants of this excess risk remain incompletely defined. The JCAD (junctional cadherin 5 associated; formerly KIAA1462) locus has been implicated in coronary artery disease through genome-wide association studies, but data in diabetic populations are scarce. Objectives: To assess whether the rs3739998 polymorphism of JCAD is associated with MI in Slovenian subjects with T2DM and to explore its relationship with coronary disease burden and coronary artery calcium (CAC). Methods: We performed a retrospective cross-sectional association study of 1471 Slovenian subjects with T2DM: 387 with prior MI and 1084 without clinical evidence of coronary artery disease. Genotyping for JCAD rs3739998 was done using a fluorescence-based competitive allele-specific PCR (KASPar). A coronary computed tomographic angiography (CCTA) substudy (n = 146) evaluated the number of diseased coronary arteries, stenosis severity, and CAC score. Results: The GG genotype was more frequently observed in MI cases compared to controls (OR 1.37; p = 0.05), and the G allele was also more prevalent among cases (OR 1.18; p = 0.05). In the CCTA substudy, no significant associations were observed between rs3739998 and the number of diseased vessels, stenosis grade, or CAC. Conclusions: In Slovenians with T2DM, the G allele and GG genotype of JCAD rs3739998 are associated with MI, supporting JCAD as a potential genetic biomarker of MI susceptibility. There was no clear relationship with anatomic disease burden or CAC, underscoring the need for replication in larger cohorts and functional studies to clarify the mechanism and clinical utility.