OBJECTIVE We tested whether a common AMPD1 gene variant is associated with
improved cardiovascular (CV) survival in patients with coronary artery dise
BACKGROUND Reduced activity of adenosine monophosphate deaminase (AMPD) may
increase production of adenosine, a cardioprotective agent. A common, nons
ense, point variant of the AMPD1 gene (C34T) results in enzymatic inactivit
y and has been associated with prolonged survival in heart failure.
METHODS Blood was collected from 367 patients undergoing coronary angiograp
hy. Genotyping was done by polymerase chain reaction amplification and rest
riction enzyme digestion, resulting in allele-specific fragments. Coronary
artery disease was defined as greater than or equal to 70% stenosis pf grea
ter than or equal to 1 coronary artery. Patients were followed prospectivel
y for up to 4.8 years. Survival statistics compared hetero- (+/-) or homozy
gotic (-/-) carriers with noncarriers.
RESULTS Patients were 66 +/- 10 years old; 79% were men; 22.6% were heteroz
ygous 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. Card
iovascular mortality was 4.4% (4/90) in AMPD1(-) allele carriers compared w
ith 11.9% (33/277) in noncarriers (p = 0.046). In multiple variable regress
ion analysis, only age (hazard ratio, 1.11/year, p < 0.001) and AMPD1(-) ca
rriage (hazard ratio, 0.36, p = 0.053) were independent predictors of CV mo
CONCLUSIONS Carriage of a common variant of the AMPD1 gene was associated w
ith improved CV survival in patients with angiographically documented CAD.
The dysfunctional AMPD1(-) allele may lead to increased cardiac adenosine a
nd increased cardioprotection during ischemic events. Adenosine monophospha
te deaminase-l genotyping should be further explored in CAD for prognostic,
mechanistic and therapeutic insights. (J Am Coil Cardiol 2000;36: 1248-52)
(C) 2000 by the American College of Cardiology.