The T2238C Human Atrial Natriuretic Peptide Molecular Variant and the Risk of Cardiovascular Diseases
AbstractAtrial 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
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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.
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. International Journal of Molecular Sciences. 2018; 19(2):540.Chicago/Turabian Style
Rubattu, Speranza; Sciarretta, Sebastiano; Marchitti, Simona; Bianchi, Franca; Forte, Maurizio; Volpe, Massimo. 2018. "The T2238C Human Atrial Natriuretic Peptide Molecular Variant and the Risk of Cardiovascular Diseases." Int. J. Mol. Sci. 19, no. 2: 540.
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