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

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 ?-carboxy-terminal peptide. In vitro, CC2238/?ANP 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 Gi? proteins. In vivo, endothelial dysfunction and increased platelet aggregation are present in human subjects carrying the C2238/?ANP allele variant. Several studies documented an increased risk of stroke and of myocardial infarction in C2238/?ANP carriers. Recently, an incomplete response to antiplatelet therapy in ischemic heart disease patients carrying the C2238/?ANP 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.

SUBMITTER: Rubattu S

PROVIDER: S-EPMC5855762 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Rubattu Speranza S Sciarretta Sebastiano S Marchitti Simona S Bianchi Franca F Forte Maurizio M Volpe Massimo M

International journal of molecular sciences 20180211 2

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-carbo ...[more]

PMID: 29439446

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Project description:The present study aimed to investigate the association between atrial natriuretic peptide (ANP) T2238C (rs5065) gene polymorphism and the risk of cardiovascular disease. Relevant literature was obtained by searching databases. The odds ratios (ORs) of the ANP T2238C locus genotype distribution in the case group of cardiovascular diseases and the control group of a non-cardiovascular population were pooled using R software. Sensitivity analysis was used to verify the stability of the results. Egger's linear regression test was used to assess the publication bias of the included literature. Studies were classified according to quality assessment score of the Newcastle-Ottawa scale, year, region, sample size and underlying disease for subgroup analysis, and meta-regression analysis was performed. A total of 12 studies comprising 45,619 patients were included. ANP rs5065 mutant gene C allele was a significant risk factor for myocardial infarction relative to T allele (OR=2.55, 95% CI=1.47-4.43, P=0.0008), CC+CT genotype was a significant risk factor for cerebrovascular events relative to TT (OR=1.14, 95% CI=1.04-1.26, P=0.0048) and the mutant CC genotype was a potential risk factor for the composite cardio-cerebral vascular events (CVE) relative to CT+TT (OR=1.40, 95% CI=0.96-2.04, P=0.081). In studies fulfilling the Hardy-Weinberg equilibrium, the CC genotype was a significant risk factor for the composite CVE relative to TT (OR=2.39, 95% CI=1.40-4.10, P=0.0018) and the CC genotype was a significant risk factor for composite CVE relative to CT+TT (OR=2.41, 95% CI=1.41-4.13, P=0.0015). The P-value of the Egger's test for publication bias was 0.436, which was not statistically significant. The results of the sensitivity analysis were relatively stable. Subgroup analysis indicated that the publication year was a potential source of heterogeneity. Regression analysis was performed for the recessive model in the composite CVE and the results showed that the study region (Europe) was one of the sources of heterogeneity (P=0.016). In conclusion, ANP 2238T/C mutation may increase the risk of myocardial infarction, cerebrovascular events and composite CVE.

Dataset Information

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

Publications

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

Similar Datasets

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