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CLINICAL STUDY: CORONARY ARTERY DISEASE

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

^a University of Utah, LDS Hospital, Salt Lake City, Utah, USA

Manuscript received December 29, 1999; revised manuscript received April 3, 2000, accepted June 2, 2000.

Reprint requests and correspondence: Dr. Jeffrey L. Anderson, University of Utah School of Medicine (4A154), Department of Medicine/Division of Cardiology, 50 North Medical Drive, Salt Lake City, Utah 84132

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 70% stenosis of 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.

Abbreviations and Acronyms   AMISTAD = Acute Myocardial Infarction Study of Adenosine   AMPD = adenosine monophosphate deaminase   CAD = coronary artery disease   CV = cardiovascular   HR = hazard ratio   MI = myocardial infarction

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