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Transcription factor 21 and coronary artery disease in a portuguese population

Session Moderated Posters Session 4

Speaker Joao Sousa

Congress : EuroPrevent 2019

  • Topic : preventive cardiology
  • Sub-topic : Prevention - Cardiovascular Risk Assessment: Biomarkers
  • Session type : Moderated Posters
  • FP Number : 392

Authors : JA Sousa (Funchal,PT), MI Mendonca (Funchal,PT), A Pereira (Funchal,PT), M Neto (Funchal,PT), J Monteiro (Funchal,PT), R Rodrigues (Funchal,PT), AC Sousa (Funchal,PT), E Henriques (Funchal,PT), S Freitas (Funchal,PT), S Borges (Funchal,PT), G Guerra (Funchal,PT), I Ornelas (Funchal,PT), A Drumond (Funchal,PT), R Palma Dos Reis (Lisbon,PT)

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Authors:
JA Sousa1 , MI Mendonca1 , A Pereira1 , M Neto1 , J Monteiro1 , R Rodrigues1 , AC Sousa1 , E Henriques1 , S Freitas1 , S Borges1 , G Guerra1 , I Ornelas1 , A Drumond1 , R Palma Dos Reis2 , 1Funchal Hospital, Research Unit, Cardiology Department - Funchal - Portugal , 2New University of Lisbon, Faculty of Medical Sciences - Lisbon - Portugal ,

Citation:

TCF21 is a member of the basic- helix-loop-helix (bHLH) transcriptor factor family being critical for embryogenesis of the heart, kidney and spleen and regulate epicardium-derived cells differentiation into smooth muscle and fibroblast lineages.

Aim: The objective of this work is to investigate the impact of TCF21 rs12190287 in the prediction and discrimination of CAD risk, individually or into a genetic risk score (GRS) formed by a set of 13 genetic variants.

Methods: We performed a case-control with 3050 subjects (1619 coronary patients and 1431 controls) from GENEMACOR study. We investigated all traditional risk factors (TRF), as well as 13 genetic variants from GWAS with unknown pathophysiological pathway so far, including TCF21 (rs12190287). These were genotyped by TaqMan Real-Time PCR method. A multiplicative genetic risk score (mGRS) has been composed. Subsequently, two logistic regressions were performed; primarily with all the TRF and then with GRS inclusion.

Results: Multivariate analysis show that, besides the strong association of the TRF with CAD risk (with smoking status on the top of the list with an OR of 3.2; p<0.0001) (Fig 1), TCF21 rs12190287 was the most significant variant from all the studied genetic set with a CAD risk of 1.5 (CI 1.1-1.9; p=0.004), followed by the well-known genetic determinant CDKN2B rs4977574 (OR 1.4  CI 1.1-1.7; p<0.002) and ZC3HC1 rs11556924 (OR 1.3  CI 1.0-1.7; p<0.034). When GRS is included to the model, all the TRF remain in the equation by the same order, and the GRS persisted as an independent genetic predictor for CAD risk (OR 1.7 CI 1.4-2.0: p<0.0001).

Conclusion: TCF21 rs12190287 is a risk factor for CAD in the Portuguese population, either individually or incorporated in GRS, independent from TRF. In the future, this can provide a new method to identify patients at higher cardiovascular risk and become a potential target for gene therapy.

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