TCF21 gene and cardiovascular events in a coronary population

Abstract Background Recent research showed that TCF21 expression in precursor cells that migrate into the disease lesions contributes to the fibrous cap, stabilizing the lesions and preventing heart attacks. Targeted deletion of the transcription factor encoded by the TCF21 was associated with vascular smooth muscle cell disruption impairing the fibrous cap structure, increasing cardiovascular(CV) disease risk. Its association with CV events is unknown. Purpose Analyze the TCF21 rs12190287 variant G>C evaluating its association with atherosclerosis severity and the appearance of cardiovascular (CV) events. Methods We performed a prospective study with 1,716 coronary artery disease (CAD) patients (mean age 53.3±7.8 years). TCF21 rs12190287 G>C was genotyped by TaqMan genotyping assay (Applied Biosystems) in all patients. The severity of CAD was graded according to the number of obstructed coronary arteries with at least 70% narrowed lumen. Chi-squared tests were used to determine differences in CAD severity by genotype. We performed a first multivariate logistic regression analysis to assess the independent risk variables associated with CAD severity. After that, we presented a second multivariate Cox regression to evaluate independent variables related to CV events. Kaplan Meier estimated the survival curves. Results 48.0% of the CC genotype carriers were associated with more than two obstructed coronary arteries compared to the GG wild genotype, which was associated with only 9.2% (p=0.002). Multivariate analysis (logistic regression) showed that the CC genotype had a high risk of CAD severity (OR=2.95; p=0.001) than GG. After Cox regression analysis, which takes into account the time to the first event, the CC genotype remained in the equation with an HR of 1.38; 95%CI 1.02-1.88; p=0.040. The survival events free at ten years is 49.1% in the CAD patients with the GG genotype, then drops to 39.6 % with the CC risk genotype. Conclusion This work shows that the GG wild genotype protects against CAD severity. In contrast, the CC genotype is associated with an increased risk of CAD severity. The patients with this allelic variant had a worse survival event free. Future research with the implementation of epigenetic and genetic therapeutics targeted to deleterious genes will allow the eradication of coronary heart disease worldwide.