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

• Published in: PloS 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
• Language: English
• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0089201

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.