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

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 causi...

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Bibliographic Details
Published inPloS one Vol. 9; no. 2; p. e89201
Main Authors Jujić, Amra, Nilsson, Peter M., Engström, Gunnar, Hedblad, Bo, Melander, Olle, Magnusson, Martin
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 19.02.2014
Public Library of Science (PLoS)
Subjects
Age Factors
Analysis
Atrial Natriuretic Factor - blood
Atrial Natriuretic Factor - genetics
Atrial natriuretic peptide
Biology
Biomarkers
Body mass
Body Mass Index
Cancer
Cancer research
Cardiac and Cardiovascular Systems
Cardiology and Cardiovascular Disease
Cardiovascular disease
Clinical Medicine
Development and progression
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - epidemiology
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Emergency medical care
Etiology
Fasting
Female
Gene polymorphism
Genetic aspects
Genotype
Glucose
Health risks
Heart failure
Hospitals
Humans
Hypertension
Insulin resistance
Kardiologi
Kardiologi och kardiovaskulära sjukdomar
Klinisk medicin
Loci
Male
Medical and Health Sciences
Medicin och hälsovetenskap
Medicine
Natriuretic peptides
Peptides
Physiology
Plasma
Plasma levels
Polymorphism
Polymorphism, Single Nucleotide - genetics
Population
Proportional Hazards Models
Public health
Regional development
Regression Analysis
Risk analysis
Risk factors
Rodents
Sex Factors
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Studies
Sweden - epidemiology
Type 2 diabetes
Sweden
Online AccessGet full text

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Abstract 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. 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). 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). 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.
AbstractList 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.
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. 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). 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). 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.
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.
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.
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.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.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).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).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).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).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.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.
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. 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). 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). 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.
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.
Audience Academic
Author Magnusson, Martin
Engström, Gunnar
Hedblad, Bo
Nilsson, Peter M.
Jujić, Amra
Melander, Olle
AuthorAffiliation 3 Center of Emergency Medicine, Skåne University Hospital, Malmö, Sweden
University of Lille Nord de France, France
1 Department of Heart Failure and Valvular Disease, Skåne University Hospital, Malmö, Sweden
2 Department of Clinical Sciences, Lund University, Malmö, Sweden
AuthorAffiliation_xml – name: 1 Department of Heart Failure and Valvular Disease, Skåne University Hospital, Malmö, Sweden
– name: 2 Department of Clinical Sciences, Lund University, Malmö, Sweden
– name: 3 Center of Emergency Medicine, Skåne University Hospital, Malmö, Sweden
– name: University of Lille Nord de France, France
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  surname: Jujić
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/24586593$$D View this record in MEDLINE/PubMed
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oai:portal.research.lu.se:publications/f85f6525-b864-48e1-acc2-d13083e4cebc$$DView record from Swedish Publication Index
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ContentType Journal Article
Copyright COPYRIGHT 2014 Public Library of Science
2014 Jujić et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2014 Jujić et al 2014 Jujić et al
Copyright_xml – notice: COPYRIGHT 2014 Public Library of Science
– notice: 2014 Jujić et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2014 Jujić et al 2014 Jujić et al
CorporateAuthor Kardiovaskulär forskning - epidemiologi
Lunds universitet
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Profilområden och andra starka forskningsmiljöer
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Internal Medicine - Epidemiology
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– name: Strategiska forskningsområden (SFO)
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– name: Lunds universitet
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– name: Lund University
– name: EXODIAB: Excellence of Diabetes Research in Sweden
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Conceived and designed the experiments: MM OM AJ. Performed the experiments: MM OM AJ BH GE PMN. Analyzed the data: MM OM AJ BH GE PMN. Contributed reagents/materials/analysis tools: MM OM AJ BH GE PMN. Wrote the paper: MM OM AJ BH GE PMN.
Competing Interests: The authors have declared that no competing interests exist.
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Snippet We have recently shown that low plasma levels of mid-regional atrial natriuretic peptide (MR-ANP) predict development of diabetes and glucose progression over...
Background We have recently shown that low plasma levels of mid-regional atrial natriuretic peptide (MR-ANP) predict development of diabetes and glucose...
BackgroundWe have recently shown that low plasma levels of mid-regional atrial natriuretic peptide (MR-ANP) predict development of diabetes and glucose...
Background We have recently shown that low plasma levels of mid-regional atrial natriuretic peptide (MR-ANP) predict development of diabetes and glucose...
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SubjectTerms Age Factors
Analysis
Atrial Natriuretic Factor - blood
Atrial Natriuretic Factor - genetics
Atrial natriuretic peptide
Biology
Biomarkers
Body mass
Body Mass Index
Cancer
Cancer research
Cardiac and Cardiovascular Systems
Cardiology and Cardiovascular Disease
Cardiovascular disease
Clinical Medicine
Development and progression
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - epidemiology
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - metabolism
Emergency medical care
Etiology
Fasting
Female
Gene polymorphism
Genetic aspects
Genotype
Glucose
Health risks
Heart failure
Hospitals
Humans
Hypertension
Insulin resistance
Kardiologi
Kardiologi och kardiovaskulära sjukdomar
Klinisk medicin
Loci
Male
Medical and Health Sciences
Medicin och hälsovetenskap
Medicine
Natriuretic peptides
Peptides
Physiology
Plasma
Plasma levels
Polymorphism
Polymorphism, Single Nucleotide - genetics
Population
Proportional Hazards Models
Public health
Regional development
Regression Analysis
Risk analysis
Risk factors
Rodents
Sex Factors
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Studies
Sweden - epidemiology
Type 2 diabetes
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Title Atrial Natriuretic Peptide and Type 2 Diabetes Development – Biomarker and Genotype Association Study
URI https://www.ncbi.nlm.nih.gov/pubmed/24586593
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https://www.proquest.com/docview/1504154267
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oai:portal.research.lu.se:publications/f85f6525-b864-48e1-acc2-d13083e4cebc
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http://dx.doi.org/10.1371/journal.pone.0089201
Volume 9
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