A genetic variant of the atrial natriuretic peptide gene is associated with left ventricular hypertrophy in a non-diabetic population – the Malmö preventive project study

Jujić, Amra; Léosdottír, Margret; Östling, Gerd; Gudmundsson, Petri; Nilsson, Peter M.; Melander, Olle; Magnusson, Martin

doi:10.1186/1471-2350-14-64

Cited by 9 publications

(7 citation statements)

References 28 publications

(35 reference statements)

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“…Cannone and associates demonstrated that the minor allele of rs5068 is associated with favorable cardiometabolic phenotype including lower BMI and waist circumference in a general US population [34], findings that were replicated in a Mediterranean population, but surprisingly no association with T2D [39]. Another possible protective role of NPs have recently been observed in our study where the minor allele of rs5068 was associated with lower left ventricular mass and lower prevalence of left ventricular hypertrophy in a population free from T2D [38].…”

Section: Introductionsupporting

confidence: 70%

Atrial Natriuretic Peptide and Type 2 Diabetes Development – Biomarker and Genotype Association Study

et al. 2014

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BackgroundWe have recently shown that low plasma levels of mid-regional atrial natriuretic peptide (MR-ANP) predict development of diabetes and glucose progression over time, independently of known risk factors for diabetes development. However, since MR-ANP levels might be influenced by unknown factors causing diabetes, we cannot rule out that such relationship might be confounded. Previous studies have shown an association of a single nucleotide polymorphism rs5068 on the natriuretic peptide precursor A (NPPA) locus gene with higher levels of circulating ANP. Since gene variants are inherited randomly and not subject to confounding, we aimed to investigate whether the variant rs5068 within the NPPA locus is associated with incident type 2 diabetes.MethodsWe genotyped the variant rs5068 within the NPPA locus in 27,307 individuals without known diabetes from the Malmö Diet Cancer Study. Incident diabetes was retrieved through national and regional registers (median follow-up time of 14 years, 2,823 incident diabetes cases).ResultsIn Cox regression analysis adjusted for age, sex and BMI, we found that the carriers of at least one copy of the G allele of rs5068 had lower likelihood of incident diabetes within 14 years (HR = 0.88, 95% CI 0.78–0.99, p = 0.037).ConclusionOur results indicate a role of the ANP system in the etiology of type 2 diabetes and might help provide insight in the metabolic actions of natriuretic peptides and the pathophysiology of type 2 diabetes.

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Section: Introductionsupporting

confidence: 70%

Atrial Natriuretic Peptide and Type 2 Diabetes Development – Biomarker and Genotype Association Study

et al. 2014

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“…15 A study conducted on a cohort of a nondiabetic Swedish population showed that subjects with the minor allele of rs5068 at the NPPA-NPPB locus, which results in higher circulating levels of ANP and BNP, 4 was associated with reduced incidence of LV hypertrophy. 16 The same genetic ANP variant also showed protection against metabolic syndrome. These findings indicate that NPs may exert multiple cardioprotective effects, mediated by NP receptors expressed in myocardium, vasculature, and in a variety of other tissues, as indicated in Figure 2.…”

Section: Natriuretic Peptides and Their Receptorsmentioning

confidence: 96%

“…In another study, deletion of 5’‐flanking region of the human NPRA gene found in Japanese patients, which reduced the transcriptional activity of the gene by 30%, appeared to increase susceptibility to hypertension and LV hypertrophy 15. A study conducted on a cohort of a nondiabetic Swedish population showed that subjects with the minor allele of rs5068 at the NPPA‐NPPB locus, which results in higher circulating levels of ANP and BNP,4 was associated with reduced incidence of LV hypertrophy 16. The same genetic ANP variant also showed protection against metabolic syndrome.…”

Section: Natriuretic Peptides and Their Receptorsmentioning

confidence: 99%

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

Kerkelä

Ulvila

Magga

2015

JAHA

128

108

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“…However, lots of candidate genes have not been confirmed in big-sample population genetic studies and Genome Wide Association Studies. In a big-sample and genome-wide meta-analysis, rs5068 variant in 3’-UTR has been inversely regulated by micro-RNA (miR)-425 and related to higher ANP levels, lower BP levels and less LV hypertrophy [ 141 ]. Rs5068 variant has also been correlated with lower anthropometric indices, lower C-reactive protein, higher high density lipoprotein, as well as less susceptibility to HF [ 142 – 144 ].…”

Section: Genetic Regulationmentioning

confidence: 99%

Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure

et al. 2018

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As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2. NPs are synthesized and secreted through certain mechanisms by cardiomyocytes, fibroblasts, endotheliocytes, immune cells (neutrophils, T-cells and macrophages) and immature cells (embryonic stem cells, muscle satellite cells and cardiac precursor cells). They are mainly produced by cardiovascular, brain and renal tissues in response to wall stretch and other causes. NPs provide natriuresis, diuresis, vasodilation, antiproliferation, antihypertrophy, antifibrosis and other cardiometabolic protection. NPs represent body's own antihypertensive system, and provide compensatory protection to counterbalance vasoconstrictor-mitogenic-sodium retaining hormones, released by renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS). NPs play central roles in regulation of heart failure (HF), and are inactivated through not only NP receptor-C, but also neutral endopeptidase (NEP), dipeptidyl peptidase-4 and insulin degrading enzyme. Both BNP and N-terminal proBNP are useful biomarkers to not only make the diagnosis and assess the severity of HF, but also guide the therapy and predict the prognosis in patients with HF. Current NP-augmenting strategies include the synthesis of NPs or agonists to increase NP bioactivity and inhibition of NEP to reduce NP breakdown. Nesiritide has been established as an available therapy, and angiotensin receptor blocker NEP inhibitor (ARNI, LCZ696) has obtained extremely encouraging results with decreased morbidity and mortality. Novel pharmacological approaches based on NPs may promote a therapeutic shift from suppressing the RAAS and SNS to re-balancing neuroendocrine dysregulation in patients with HF. The current review discussed the synthesis, secretion, function and metabolism of NPs, and their diagnostic, therapeutic and prognostic values in HF.

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A genetic variant of the atrial natriuretic peptide gene is associated with left ventricular hypertrophy in a non-diabetic population – the Malmö preventive project study

Cited by 9 publications

References 28 publications

Atrial Natriuretic Peptide and Type 2 Diabetes Development – Biomarker and Genotype Association Study

Atrial Natriuretic Peptide and Type 2 Diabetes Development – Biomarker and Genotype Association Study

Natriuretic Peptides in the Regulation of Cardiovascular Physiology and Metabolic Events

Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure

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