Transcription factor 21 and prognosis in a coronary population

Abstract

Introduction TCF21 is a member of the basic helix-loop-helix (bHLH) transcriptor factor family, being critical for embryogenesis of the heart. It regulates epicardium-derived cells differentiation into smooth muscle (SMC) and fibroblast lineages. The biological roles of TCF21 in epicardial fate determination and the progression of atherosclerosis remains a controversial issue. Purpose Investigate the impact of the TCF21 rs12190287 G>C variant on the prognosis of a coronary artery disease (CAD) cohort. Methods A prospective study was performed with 1,713 CAD patients (mean age 53.3±7.8; 78.7% male) surveyed in terms of MACE occurrence in an extended follow-up of 5.0±4.3. TCF21 rs12190287 was genotyped and analysed using the dominant model (GC+CC) and, subsequently, compared with the wild-type GG to evaluate the survival probability by Kaplan-Meier. A Cox regression analysis with all the risk factors and genetic models was performed to assess the independent variables associated with the prognosis of CAD patients. Results GG wild genotype was present in 9.5% of the population, GC in 43.2% and the risk genotype CC accounted for 47.3% of the CAD patients. The dominant model GC+CC showed a worse survival throughout the follow-up period. After multivariate Cox regression analysis, this model remained in the equation as an independent risk factor for MACE occurrence with an HR of 1.41 (p=0.033) together with multivessel disease, physical inactivity, chronic kidney disease (CKD) and diabetes. Conclusion TCF21 rs12190287 is a risk factor for prognosis in our population. The role of this gene may influence fundamental SMC processes in response to vascular stress, accelerating atherosclerosis progression and may represent a target for future therapies. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM