Genetics links between transforming growth factor β pathway and coronary disease

Recent genome-wide association studies broadened our view on the complex genetic roots of coronary artery disease (CAD). The subsequent challenge is now to elucidate the mechanisms linking genetic variants with disease risk. Here, we focus on the transforming growth factor beta (TGF-β) pathway and review genetic as well as comprehensive annotation and systems biology analyses to provide further links between TGF-β, the SMAD family and CAD risk. Indeed, it has long been shown that the TGF-β signaling pathway plays a role in the pathophysiology of endothelial and vascular smooth muscle cells. Nevertheless, the precise mechanisms leading to CAD are still vague, due to the vast number of mediated effects and multi-functional and context-dependent biology of the TGF-β signaling. While previous reviews addressed these issues, less attention was paid to the genetic underpinnings in the signaling process, which are of parallel importance and essence regarding the transduction and functioning of the whole pathway. Here, we provide an overview of how the so far identified genetic risk loci are involved in the regulation of the canonical TGF-β - SMAD signaling pathway, which might give further mechanistic insights into CAD risk.