Coronary artery disease patients with rs7904519 (TCF7L2) are at a persistent risk of type 2 diabetes

Aims: Type 2 diabetes (T2D) and coronary artery disease (CAD) often coexist and share genetic factors. This study aimed to investigate the common genetic factors underlying T2D and CAD in patients with CAD. Methods: A three-step association approach was conducted: a) a discovery step involving 943 CAD patients with T2D and 1,149 CAD patients without T2D; b) an eliminating step to exclude CAD or T2D specific variants; and c) a replication step using the UK Biobank data. Results: Ten genetic loci were associated with T2D in CAD patients. Three variants were specific to either CAD or T2D. Five variants lost significance after adjusting for covariates, while two SNPs remained associated with T2D in CAD patients (rs7904519G: TCF7L2 and rs17608766C: GOSR2). The T2D susceptibility rs7904519G was associated with increased T2D risk, while the CAD susceptibility rs17608766C was negatively associated with T2D in CAD patients. These associations were replicated in a UK Biobank data, confirming the results. Conclusions: No significant common T2D and CAD susceptibility genetic association was demonstrated indicating distinct disease pathways. However, CAD patients carrying the T2D susceptibility gene TCF7L2 remain at higher risk for developing T2D emphasizing the need for frequent monitoring in this subgroup.