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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. 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. 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 (rs7904519*G: TCF7L2 and rs17608766*C: GOSR2). The T2D susceptibility rs7904519*G was associated with increased T2D risk, while the CAD susceptibility rs17608766*C was negatively associated with T2D in CAD patients. These associations were replicated in a UK Biobank data, confirming the results. 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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Coronary artery disease (CAD) is a multifactorial disease with acquired and inherited components. Aim: We investigated the roles of family history and consanguinity on CAD risk and age at diagnosis in 4284 patients. The compounded impact of diabetes, hyperlipidemia, hypertension, smoking, and BMI, which are known CAD risk factors, on CAD risk and age at diagnosis was also explored. Methods: CAD was determined by cardiac catheterization. Logistic regression and stratification were performed to determine the impact of family history and consanguinity on risk and onset of CAD, controlling for diabetes, hyperlipidemia, hypertension, smoking, and BMI. Results: Family history of CAD and gender significantly increased the risk for young age at diagnosis of CAD (p <0.001). Consanguinity did not promote risk of CAD (p =0.38), but did affect age of disease diagnosis (p <0.001). The mean age at disease diagnosis was lowest, 54.8 years, when both family history of CAD and consanguinity were considered as unique risk factors for CAD, compared to 62.8 years for the no-risk-factor patient category (p <0.001). Conclusions: Family history of CAD and smoking are strongly associated with young age at diagnosis. Furthermore, parental consanguinity in the presence of family history lowers the age of disease diagnosis significantly for CAD, emphasizing the role of strong genetic and cultural CAD modifiers. These findings highlight the increased role of genetic determinants of CAD in some population subgroups, and suggest that populations and family structure influence genetic heterogeneity between patients with CAD. [ABSTRACT FROM AUTHOR]