title: Atrial natriuretic peptide and type 2 diabetes development--biomarker and genotype association study.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Heart Failure and Valvular Disease, Skåne University Hospital, Malmö, Sweden ; Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Amra
authors.initials: A
authors.lastname: Jujić
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden ; Center of Emergency Medicine, Skåne University Hospital, Malmö, Sweden.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Nilsson
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Engström
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Hedblad
authors.affiliation: Department of Clinical Sciences, Lund University, Malmö, Sweden ; Center of Emergency Medicine, Skåne University Hospital, Malmö, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.affiliation: Department of Heart Failure and Valvular Disease, Skåne University Hospital, Malmö, Sweden ; Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Magnusson
mesh_terms: D000367:Age Factors; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012737:Sex Factors; D013548:Sweden / Q000453:epidemiology
chemical_list: C472955:NPPA protein, human; D009320:Atrial Natriuretic Factor