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Analysis of endothelin-1 and endothelin-1 receptor A gene polymorphisms in patients with pulmonary arterial hypertension

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Abstract

This study analyses the frequency and the potential role of two polymorphisms, the +134del/insA, located in the gene encoding for Endothelin-1 (EDN1), and the His323His in the gene encoding for Endothelin receptor type A (EDNRA) in a cohort of 98 consecutive patients with pulmonary arterial hypertension from two different Cardiology Units (Mid-South of Italy), and in 100 healthy Caucasian subjects randomly recruited from the same area. Cardiac anatomy and function were analysed by non invasive diagnostic imaging techniques (Echocardiography standard m-mode, 2D, colour-Doppler) and by invasive studies (cardiac catheterization). Molecular screening of the region of interest was performed by automated sequencing. At univariate analysis, patients with the His323His TT genotype show a lower cardiac index (2 ± 0.6 vs. 2.3 ± 0.6; p = 0.05) and a higher indexed pulmonary vascular resistance (18.8 ± 9.6 vs. 14.2 ± 6.9; p = 0.01) at cardiac catheterization. A logistic multivariate model shows idiopathic disease (p = 0.01; OR = 3.8; CI = 1.3–11) and indexed pulmonary vascular resistances (p = 0.01; OR = 1.1; CI = 1–1.2) as independent predictors of TT genotype. Our findings may suggest a potential link between specific genotypes in the EDNRA gene and susceptibility for PAH.

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Acknowledgments

We express our gratitude to all the nurses of the Division of Paediatric and Adult Cardiology, Monaldi Hospital, for the technical support and cooperation in the outpatient clinic, particularly Mrs Assunta Carandente, Mrs Antonella Nannolo, Mrs Assunta Di Vaio, and Mrs Debora De Santis. This work was supported in part by Grants to Prof. Calabrò R.from the Actelion Pharmaceuticals Italia SRL. (2008).

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Authors and Affiliations

  1. Division of Cardiology, Monaldi Hospital, Second University of Naples, Via L. Bianchi, 80131, Naples, Italy

    Paolo Calabrò, Giuseppe Limongelli, Michele D’Alto, Paola Argiento, Emanuele Romeo, Giuseppe Pacileo, Maria Giovanna Russo & Raffaele Calabrò

  2. Cardiovascular Genetic and Molecular Laboratory, Monaldi Hospital, Second University of Naples, Naples, Italy

    Paolo Calabrò, Giuseppe Limongelli, Valeria Maddaloni, Raffaella D’Alessandro, Brunella Ziello & Raffaele Calabrò

  3. Pulmonary Hypertension Unit, Department of Cardiovascular and Respiratory Diseases, La Sapienza University, Rome, Italy

    Carmine Dario Vizza, Roberto Poscia, Roberto Badagliacca & Francesco Fedele

Authors
  1. Paolo Calabrò
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  2. Giuseppe Limongelli
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  3. Valeria Maddaloni
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  4. Carmine Dario Vizza
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  5. Michele D’Alto
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  6. Raffaella D’Alessandro
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  7. Roberto Poscia
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  8. Paola Argiento
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  9. Brunella Ziello
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  10. Roberto Badagliacca
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  11. Emanuele Romeo
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  12. Giuseppe Pacileo
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  13. Maria Giovanna Russo
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  14. Francesco Fedele
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  15. Raffaele Calabrò
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Corresponding author

Correspondence to Paolo Calabrò.

Additional information

P. Calabrò and G. Limongelli equally contributed to this manuscript.

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Calabrò, P., Limongelli, G., Maddaloni, V. et al. Analysis of endothelin-1 and endothelin-1 receptor A gene polymorphisms in patients with pulmonary arterial hypertension. Intern Emerg Med 7, 425–430 (2012). https://doi.org/10.1007/s11739-011-0643-2

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  • DOI: https://doi.org/10.1007/s11739-011-0643-2

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