title: A common variant of the AMPD1 gene predicts improved cardiovascular survival in patients with coronary artery disease.
abstract: OBJECTIVE
  We tested whether a common AMPD1 gene variant is associated with improved cardiovascular (CV) survival in patients with coronary artery disease (CAD).
  
  
  BACKGROUND
  Reduced activity of adenosine monophosphate deaminase (AMPD) may increase production of adenosine, a cardioprotective agent. A common, nonsense, point variant of the AMPD1 gene (C34T) results in enzymatic inactivity and has been associated with prolonged survival in heart failure.
  
  
  METHODS
  Blood was collected from 367 patients undergoing coronary angiography. Genotyping was done by polymerase chain reaction amplification and restriction enzyme digestion, resulting in allele-specific fragments. Coronary artery disease was defined as > or =70% stenosis of > or =1 coronary artery. Patients were followed prospectively for up to 4.8 years. Survival statistics compared hetero- (+/-) or homozygotic (-/-) carriers with noncarriers.
  
  
  RESULTS
  Patients were 66 +/- 10 years old; 79% were men; 22.6% were heterozygous and 1.9% homozygous for the variant AMPD1(-) allele. During a mean of 3.5 +/- 1.0 years, 52 patients (14.2%) died, 37 (10.1%) of CV causes. Cardiovascular mortality was 4.4% (4/90) in AMPD1(-) allele carriers compared with 11.9% (33/277) in noncarriers (p = 0.046). In multiple variable regression analysis, only age (hazard ratio, 1.11/year, p < 0.001) and AMPD1(-) carriage (hazard ratio, 0.36, p = 0.053) were independent predictors of CV mortality.
  
  
  CONCLUSIONS
  Carriage of a common variant of the AMPD1 gene was associated with improved CV survival in patients with angiographically documented CAD. The dysfunctional AMPD1(-) allele may lead to increased cardiac adenosine and increased cardioprotection during ischemic events. Adenosine monophosphate deaminase-1 genotyping should be further explored in CAD for prognostic, mechanistic and therapeutic insights.
authors.affiliation: Department of Medicine, University of Utah School of Medicine, LDS Hospital, Salt Lake City 84132, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Anderson
authors.forename: J
authors.initials: J
authors.lastname: Habashi
authors.forename: J F
authors.initials: JF
authors.lastname: Carlquist
authors.forename: J B
authors.initials: JB
authors.lastname: Muhlestein
authors.forename: B D
authors.initials: BD
authors.lastname: Horne
authors.forename: T L
authors.initials: TL
authors.lastname: Bair
authors.forename: R R
authors.initials: RR
authors.lastname: Pearson
authors.forename: N
authors.initials: N
authors.lastname: Hart
mesh_terms: D000659:AMP Deaminase / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000483:Alleles; D018389:Codon, Nonsense / Q000235:genetics* / Q000378:metabolism; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics / Q000401:mortality*; D004247:DNA / Q000032:analysis*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D018389:Codon, Nonsense; D017931:DNA Primers; D005819:Genetic Markers; D004247:DNA; D000659:AMP Deaminase