A common variant of the AMPD1 gene predicts improved cardiovascular survival in patients with coronary artery disease

J Am Coll Cardiol. 2000 Oct;36(4):1248-52. doi: 10.1016/s0735-1097(00)00850-0.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • AMP Deaminase / genetics*
  • AMP Deaminase / metabolism
  • Aged
  • Alleles
  • Codon, Nonsense / genetics*
  • Codon, Nonsense / metabolism
  • Coronary Angiography
  • Coronary Disease / diagnostic imaging
  • Coronary Disease / enzymology
  • Coronary Disease / genetics
  • Coronary Disease / mortality*
  • DNA / analysis*
  • DNA Primers / chemistry
  • Female
  • Genetic Markers
  • Genotype
  • Humans
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics
  • Prognosis
  • Prospective Studies
  • Survival Rate


  • Codon, Nonsense
  • DNA Primers
  • Genetic Markers
  • DNA
  • AMP Deaminase