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TCF21 variant is a risk factor for coronary artery disease and will it be a prognostic marker?
Session:
Painel 12- Prevenção / Reabilitação Cardíaca 2
Speaker:
Margarida Temtem
Congress:
CPC 2020
Topic:
J. Preventive Cardiology
Theme:
28. Risk Factors and Prevention
Subtheme:
28.2 Risk Factors and Prevention – Cardiovascular Risk Assessment
Session Type:
Posters
FP Number:
---
Authors:
Margarida Temtem; Marco Serrão; Andreia Pereira; Marina Santos; Flávio Mendonça; Joao Adriano Sousa; Joel Monteiro; Ana Célia Sousa; Sónia Freitas; Eva Henriques; Graça Guerra; Ilídio Ornelas; A. Drumond de Freitas; Roberto Palma dos Reis; Maria Isabel Mendonça
Abstract
<p><strong>Background</strong>: TCF21 gene, encodes a basic-helix- loop- helix transcription factor, playing a critical action in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Recent data suggest that TCF21 may play a role in the state of differentiation of SMC precursor cells that migrate to vascular lesions and contribute to fibrous cap.</p> <p><strong>Objectives:</strong> Investigate the association of TCF21 rs12190287G>C variant with coronary artery disease (CAD) in a Portuguese population and its role on the prognosis.</p> <p><strong>Methods</strong>: Case-control study with 3120 participants, 1687 coronary patients with at least 75% obstruction of a major coronary artery and 1433 controls. Genotyping used the TaqMan technique (Applied Biosystems) and then a univariate and multivariate logistic regression analysis were performed. After a mean follow-up of 5.01±4.2 years (interquartile range 1.96-7.57), the occurrence of the combined Major Adverse Cardiovascular Events (MACE) (Cardiovascular Mortality, non-fatal Myocardial Infarction, new Revascularization, Cerebrovascular Disease and Peripheric Vascular Disease) were registered and analysed by Cox regression. Finally, Kaplan-Meier survival estimate was performed.</p> <p><strong>Results: </strong>In the total population, GC+CC genotype was found to be associated with CAD with an OR of 1.285; CI:1.022-1.614; p=0.031. After multivariate logistic regression, adjusted to traditional risk factors, the association with CAD remained significant for this genotype (OR=1.340; CI:1.042-1.723; p=0.022). After Cox regression adjusted for confounding variables (age and sex, hypertension, diabetes, smoking, dyslipidemia, eGFR, Ejection fraction<55) the mutated genotype remained a significant predictor of MACE (HR=1.420; CI: 1.032-1.953; p=0.031). The individuals carrying the mutated allele (GC+CC) at the mean follow-up showed an event probability of 36.1%, whereas the wild population (GG) presented only 23.4%. The Log-Rank test showed significant differences between the two curves (p=0.019).</p> <p><strong>Conclusion:</strong> The mutated TCF21 variant can provide a new marker to identify patients at high cardiovascular risk and may represent a potential target for gene therapy in future.</p>
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