Predilection of CHRNA5 SNP to smoking-related cardiotoxicity

Cigarette smoking, the leading cause of preventable deaths, is responsible for nearly half a million deaths per year in the United States. Evidence has shown that smoking can cause diseases of nearly all organs of the body with the greatest morbidity and mortality in the lung and heart. It is clear that smoking increases the risk of cardiovascular disease, whereas how smoking worsens the heart function remains poorly understood. In addition, different smokers are projected to develop smoking-related cardiovascular disease with a diverse severity and speed of progress. These facts suggest that individual unique genetic factor and smoking play a combinatorial role in the development of cardiovascular disease. However, this theory is difficult to prove previously due to the lack of human heart samples. With the advent of patient specific induced pluripotent stem cells which can be differentiated into heart muscle cells, investigation of smoking-related cardiac dysfunction with human genetic background becomes feasible. The key objective of this TRDRP postdoc fellowship proposal is to elucidate the genetic impact on the initiation and development of smoking-related cardiac dysfunction at the cellular level. The outcomes of this research will provide a strong evidence that genetic biomarkers can be used for early detection of smoking-related cardiovascular disease. Furthermore, this research project will offer a proof-of-principle for using induced pluripotent stem cell platform to screen potential compounds for treatment of smoking-related cardiovascular disease.