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Int. J. Mol. Sci. 2018, 19(2), 540; https://doi.org/10.3390/ijms19020540

The T2238C Human Atrial Natriuretic Peptide Molecular Variant and the Risk of Cardiovascular Diseases

1
Department of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, S. Andrea Hospital, via di Grottarossa 1035, 00189 Rome, Italy
2
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Località Camerelle, 86077 Pozzilli (Is), Italy
3
Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy
*
Author to whom correspondence should be addressed.
Received: 25 January 2018 / Revised: 7 February 2018 / Accepted: 10 February 2018 / Published: 11 February 2018
(This article belongs to the Special Issue Role of Genomics in the Management of Hypertension)
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Abstract

Atrial natriuretic peptide (ANP) is a cardiac hormone which plays important functions to maintain cardio-renal homeostasis. The peptide structure is highly conserved among species. However, a few gene variants are known to fall within the human ANP gene. The variant rs5065 (T2238C) exerts the most substantial effects. The T to C transition at the 2238 position of the gene (13–23% allele frequency in the general population) leads to the production of a 30-, instead of 28-, amino-acid-long α-carboxy-terminal peptide. In vitro, CC2238/αANP increases the levels of reactive oxygen species and causes endothelial damage, vascular smooth muscle cells contraction, and increased platelet aggregation. These effects are achieved through the deregulated activation of type C natriuretic peptide receptor, the consequent inhibition of adenylate cyclase activity, and the activation of Giα proteins. In vivo, endothelial dysfunction and increased platelet aggregation are present in human subjects carrying the C2238/αANP allele variant. Several studies documented an increased risk of stroke and of myocardial infarction in C2238/αANP carriers. Recently, an incomplete response to antiplatelet therapy in ischemic heart disease patients carrying the C2238/αANP variant and undergoing percutaneous coronary revascularization has been reported. In summary, the overall evidence supports the concept that T2238C/ANP is a cardiovascular genetic risk factor that needs to be taken into account in daily clinical practice. View Full-Text
Keywords: atrial natriuretic peptide; T2238C variant; endothelial dysfunction; smooth muscle cells contraction; platelet aggregation; epigenetics; cardiovascular diseases atrial natriuretic peptide; T2238C variant; endothelial dysfunction; smooth muscle cells contraction; platelet aggregation; epigenetics; cardiovascular diseases
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Rubattu, S.; Sciarretta, S.; Marchitti, S.; Bianchi, F.; Forte, M.; Volpe, M. The T2238C Human Atrial Natriuretic Peptide Molecular Variant and the Risk of Cardiovascular Diseases. Int. J. Mol. Sci. 2018, 19, 540.

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