title: Influence of rs5065 atrial natriuretic peptide gene variant on coronary artery disease.
abstract: OBJECTIVE
  The aim of this study was to investigate the impact of rs5065 atrial natriuretic peptide (ANP) gene variant on coronary artery disease (CAD) and its outcomes and to gain potential mechanistic insights on the association with CAD.
  
  
  BACKGROUND
  Either modified ANP plasma levels or peptide structural alterations have been involved in development of cardiovascular events.
  
  
  METHODS
  Three hundred ninety-three control subjects and 1,004 patients undergoing coronary angiography for suspected CAD (432 stable angina [SA], 572 acute coronary syndrome [ACS]) were genotyped for rs5065 ANP gene variant. Data in SA and ACS groups were replicated in an independent population of 482 stable angina patients (rSA) and of 675 ACS patients, respectively. Clinical follow-up was available for both SA and rSA patients. Plasma N-terminal-proANP, myeloperoxidase, lipoprotein-associated phospholipase A2, and oxidized low-density lipoprotein were assessed in a subgroup of rSA patients.
  
  
  RESULTS
  rs5065 minor allele (MA) was an independent predictor of ACS (odds ratio: 1.90; 95% confidence interval: 1.40 to 2.58, p < 0.001). At follow-up, rs5065 MA was independently associated with a significantly higher rate of major adverse cardiovascular events in the SA group, p < 0.001. Data were replicated in the rSA group at follow-up (p = 0.008). Cox proportional hazard analysis tested by 4 models confirmed higher major adverse cardiovascular events risk in rs5065 MA carriers in both SA and rSA cohorts. Significantly higher myeloperoxidase levels were detected in rs5065 MA carriers (n = 597 [345 to 832 μg/l] vs. n = 488 [353 to 612 μg/l], p = 0.038). No association of rs5065 was observed with N-terminal-proANP levels.
  
  
  CONCLUSIONS
  The MA of rs5065 ANP gene variant associates with increased susceptibility to ACS and has unfavorable prognostic value in CAD.
authors.affiliation: Cardiovascular Center Aalst, OLV Clinic, Aalst, Belgium.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Barbato
authors.forename: Jozef
authors.initials: J
authors.lastname: Bartunek
authors.forename: Fabio
authors.initials: F
authors.lastname: Mangiacapra
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Sciarretta
authors.forename: Rosita
authors.initials: R
authors.lastname: Stanzione
authors.forename: Leen
authors.initials: L
authors.lastname: Delrue
authors.forename: Maria
authors.initials: M
authors.lastname: Cotugno
authors.forename: Simona
authors.initials: S
authors.lastname: Marchitti
authors.forename: Guido
authors.initials: G
authors.lastname: Iaccarino
authors.forename: Giusy
authors.initials: G
authors.lastname: Sirico
authors.forename: Sara
authors.initials: S
authors.lastname: Di Castro
authors.forename: Anna
authors.initials: A
authors.lastname: Evangelista
authors.forename: Diether
authors.initials: D
authors.lastname: Lambrechts
authors.forename: Peter
authors.initials: P
authors.lastname: Sinnaeve
authors.forename: Bernard
authors.initials: B
authors.lastname: De Bruyne
authors.forename: Frans
authors.initials: F
authors.lastname: Van De Werf
authors.forename: Stefaan
authors.initials: S
authors.lastname: Janssens
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: William
authors.initials: W
authors.lastname: Wijns
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000502:physiology; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011446:Prospective Studies
chemical_list: D005819:Genetic Markers; D009320:Atrial Natriuretic Factor