Abstract 819: Type 2 Diabetes Significantly Modulates the Impact of TCF7L2 Variant rs7903146 on the Risk of Coronary Atherosclerosis
Background: Coronary artery disease (CAD) is the most frequent cause of death in type 2 diabetes (T2DM), and CAD shares common risk factors with T2DM. Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146, increase T2DM risk. Potential associations between TCF7L2 variant rs7903146 and coronary atherosclerosis are unknown. We therefore addressed the association between rs7903146 and angiographically determined CAD.
Methods: We genotyped variant rs7903146 in a large cohort of 1595 consecutive Caucasian patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. Significant CAD was diagnosed in the presence of coronary stenoses with lumen narrowing ≥50%.
Results: Variant rs7903146 in the total study cohort was significantly associated with significant CAD (adjusted additive odds ratio (OR) 1.27 [1.07–1.51]; p=0.006). This association was strong and significant in T2DM patients (n=373; OR=1.81 [1.25–2.63]; p=0.002) but not in non-diabetic subjects (OR=1.10 [0.90 –1.34]; p=0.354). The interaction term risk allele by T2DM was significant (p=0.006), indicating a significantly stronger impact of the polymorphism on CAD in T2DM patients than in non-diabetic subjects. Further, the association of variant rs7903146 with T2DM depended on the presence of CAD: The polymorphism strongly predicted T2DM in patients with significant CAD (OR=1.55 [1.23–1.94]; p<0.001) but not in subjects without significant CAD (OR=1.10 [0.77–1.57]; p=0.613; pinteraction=0.037).
Conclusions: We conclude that TCF7L2 variant rs7903146 is significantly associated with angiographically diagnosed CAD and that this association is significantly modulated by the presence of T2DM. Furthermore, the impact of rs7903146 on T2DM risk is significantly modulated by the presence of CAD.