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. 2014 Feb 19;9(2):e89201.
doi: 10.1371/journal.pone.0089201. eCollection 2014.

Atrial natriuretic peptide and type 2 diabetes development--biomarker and genotype association study

Amra Jujić  1 , Peter M Nilsson  2 , Gunnar Engström  3 , Bo Hedblad  3 , Olle Melander  2 , Martin Magnusson  1
Affiliations

Atrial natriuretic peptide and type 2 diabetes development--biomarker and genotype association study

Amra Jujić et al. PLoS One. .

Abstract

Background: We 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.

Methods: We 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).

Results: In 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).

Conclusion: Our 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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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Risk of diabetes occurring in a AA versus AG+GG model of rs5068 allele.
Cumulative incidence of T2D over a mean follow-up of 14 years for major allele (AA) and G allele (AG+GG) of rs5068. * Follow up period in years until first diabetes event, or, for censored cases, death, emigration or last follow up date.
See this image and copyright information in PMC

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Grants and funding

Drs. Magnusson and Melander were supported by grants from the Swedish Medical Research Council (http://www.vr.se/inenglish.4.12fff4451215cbd83e4800015152.html), the Swedish Heart and Lung Foundation (http://www.hjart-lungfonden.se/Om-Hjart-lungfonden/About-HLF/), the Medical Faculty of Lund University, Skåne University Hospital, the Albert Påhlsson Research Foundation (ams.orbelon.com), the Crafoord Foundation (www.crafoord.se), the Ernhold Lundströms Research Foundation (https://www.mah.se/PageFiles/3463/Microsoft%20Word%20-%20Kung%C3%B6relse%202011.pdf), the Region Skåne (http://www.skane.se/), the Hulda and Conrad Mossfelt Foundation, the Southwest Skanes Diabetes Foundation, the King Gustaf V and Queen Victoria Foundation, the Lennart Hanssons Memorial Fund (http://www.hypertoni.org/stadgar_lennart_hanssons_mem.htm), Knut and Alice Wallenberg Foundation (http://www.wallenberg.com/kaw/), and the Marianne and Marcus Wallenberg Foundation. Drs. Nilsson and Hedblad were supported by grants from the Swedish Medical Research Council and the Swedish Heart and Lung Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.