Abstract: P1256 TYPE 2 DIABETES SIGNIFICANTLY MODULATES THE IMPACT OF TCF7L2 RS7903146 VARIANT ON THE RISK OF CORONARY ATHEROSCLEROSIS

Abstract

Results: Variations in the transcription factor 7-like 2 (TCF7L2) gene, particularly rs7903146 impair beta-cell function and increase the risk of type 2 diabetes (T2DM). Coronary artery disease (CAD) is the most frequent cause of death in T2DM patients, and CAD shares common risk factors with T2DM. Potential associations between TCF7L2 variant rs7903146 and coronary atherosclerosis are unknown. We addressed the association between rs7903146 and CAD in a large cohort of 1595 consecutive Caucasian patients undergoing coronary angiography for the evaluation of stable CAD. An additive model of inheritance was used; significant CAD was diagnosed in the presence of coronary stenoses ≥50%. The prevalence of T2DM significantly increased from homozygous carriers of the frequent allele over heterozygous subjects to those who were homozygous for the rare allele (20.3%, 24.9%, and 31.3%; ptrend=0.001). In the total study cohort, variant rs7903146 was significantly associated with the presence of significant CAD (adjusted odds ratio (OR) 1.27 [1.06-1.51]; p=0.008). Importantly, subgroup analyses with respect to the presence of T2DM showed a strong and significant association between variant rs7903146 and significant CAD in T2DM patients (n=373; OR=1.84 [1.27-2.68]; p=0.001), whereas in non-diabetic subjects (n = 1222), variant rs7903146 was not associated with significant CAD (OR=1.08 [0.88-1.32]; p=0.446). An interaction term T2DM x rs7903146 was significant (p=0.004), indicating that this variant had a significantly stronger impact on CAD in patients with T2DM than in non-diabetic individuals. We conclude that T2DM significantly modulates the impact of TCF7L2 rs7903146 variant on angiographically characterized coronary atherosclerosis.