Mice with a coronary artery disease-linked mutation in Wnt-coreceptor LRP6 (LDL receptor-related protein 6) exhibit vascular smooth muscle cell dedifferentiation and obstructive coronary artery disease, which are paradoxically associated with reduced TCF7L2 expression.
We genotyped TCF7L2 variants rs7903146, rs12255372, and rs11196205 in a cross-sectional study including 1,650 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD.
Moreover, we observed associations between TCF7L2 variants and the following diabetic complications: diabetic retinopathy, cardiovascular disease and coronary artery disease.
In T2D-specific PPI networks involving 64 genes, TCF7L2 (Degree = 169) was identified as a key gene in T2D development, while in CAD-specific PPI networks involving 64 genes, HIF1A (Degree = 124), SMAD1 (Degree = 112) and SKIL (Degree = 94) were identified as key genes in the CAD development.
TCF7L2rs7903146 T allele is associated with a 1.57 increased risk for type 2 diabetes in a Brazilian cohort of patients with known coronary heart disease.