Beyond Coronary Obstruction: Genome-Wide Copy Number Variation Profiling in MINOCA and Atherosclerotic Acute Coronary Syndrome

Background and Objectives: The genetic architecture underlying myocardial infarction with nonobstructive coronary arteries (MINOCA) remains incompletely understood. While genetic research in coronary artery disease has largely focused on individual variants and susceptibility loci, genome-wide structural genomic alterations have received limited attention. We aimed to characterize and compare copy number variation (CNV) profiles in patients with MINOCA and atherosclerotic acute coronary syndrome (ACS) using high-resolution molecular karyotyping. Materials and Methods: This observational study included 83 patients with myocardial infarction, comprising 39 with MINOCA and 44 with atherosclerotic ACS. Genome-wide molecular karyotyping was performed using the CytoScan HT-CMA 1000K chromosomal microarray platform(Thermo Fisher Scientific, Waltham, MA, USA). Genomic gains and losses were systematically characterized according to their chromosomal location, recurrence, and associated gene annotations, enabling a comprehensive comparison of structural genomic patterns between the two clinical phenotypes. Results: Genome-wide analysis identified 221 CNV events, including 109 in MINOCA and 112 in atherosclerotic ACS. Copy number gains accounted for 65 and 78 events, respectively, whereas losses accounted for 44 and 34 events. Recurrent alterations involved 17q21.31, 19p12, and 2q37.3, revealing shared structural genomic patterns across both phenotypes. Notably, distinct CNV regions were identified exclusively in MINOCA, including 6q24.1, 4q13.3, and 17q11.2, with the latter encompassing genes involved in inflammatory and cellular signaling pathways. Other recurrent alterations, including 8q24.13 and 16q21, were observed exclusively in atherosclerotic ACS. Conclusions: High-resolution genome-wide molecular karyotyping revealed a complex landscape of shared and distinct structural genomic alterations in MINOCA and atherosclerotic ACS. These findings highlight candidate genomic regions that may provide new insights into the biological heterogeneity of myocardial infarction and its underlying mechanisms.