title: Evaluation of non-synonymous NPPA single nucleotide polymorphisms in atrial fibrillation.
abstract: OBJECTIVE
  Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is an important cause of morbidity and mortality. A genetic mutation in the NPPA gene, which encodes the atrial natriuretic peptide, has been identified as the putative causative factor in a family with an autosomal dominant pattern of inheritance for AF. Two common single nucleotide polymorphisms (SNPs) in NPPA, rs5063 and rs5065, result in amino acid changes of the primary peptide and have been previously implicated in conditions associated with AF, including stroke and hypertension. Recently, the rs5063 SNP has been reported to confer an increased risk of AF development in a Chinese population. We sought to examine the associations of both rs5063 and rs5065 with AF in two separate North American cohorts of European ancestry.
  
  
  RESULTS
  Patients with early-onset AF, along with healthy controls, were recruited at the University of Ottawa Heart Institute (UOHI) and the Massachusetts General Hospital (MGH). Study participants were genotyped for rs5063 and rs5065 using a combination of restriction fragment length polymorphism analysis and DNA microarrays. The study genotyped a total of 620 AF cases and 2446 healthy controls. The UOHI arm of the study identified an odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.42-1.24] for rs5063, whereas an OR of 1.33 (95% CI: 0.80-2.21) was observed in the MGH arm. The combined OR approximated unity (OR 0.99; 95% CI: 0.54-1.80). Analysis of rs5065 revealed an OR of 1.12 (95% CI: 0.84-1.48) in UOHI, 1.08 (95% CI 0.80-1.45) in MGH, and 1.10 (95% CI 0.90-1.35) when combined.
  
  
  CONCLUSIONS
  Common non-synonymous genetic variants within NPPA in these two large North American cohorts of European ancestry are not associated with the development of AF.
authors.affiliation: Arrhythmia Research Laboratory, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON, Canada.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Roberts
authors.forename: Robert W
authors.initials: RW
authors.lastname: Davies
authors.forename: Steven A
authors.initials: SA
authors.lastname: Lubitz
authors.forename: Isabelle L
authors.initials: IL
authors.lastname: Thibodeau
authors.forename: Pablo B
authors.initials: PB
authors.lastname: Nery
authors.forename: David H
authors.initials: DH
authors.lastname: Birnie
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Robert
authors.initials: R
authors.lastname: Lemery
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Ellinor
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gollob
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000208:ethnology* / Q000235:genetics*; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011499:Protein Processing, Post-Translational / Q000502:physiology; D044465:White People / Q000706:statistics & numerical data*
chemical_list: C472955:NPPA protein, human; D009320:Atrial Natriuretic Factor