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(Circulation. 1999;99:1422-1425.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Common Variant in AMPD1 Gene Predicts Improved Clinical Outcome in Patients With Heart Failure
From the Cardiovascular Division (E.L., P.D.M., D.D., J.L.S.), Department of Medicine (E.L., P.D.M., D.D., J.L.S., E.W.H.), and Department of Biostatistics and Epidemiology (T.R.R.), Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, Pa.
Correspondence to Evan Loh, MD, Cardiovascular Division, 9 Founders Pavilion, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. E-mail lohe{at}mail.med.upenn.edu
Background—This study was undertaken to identify gene(s) that may be associated with improved clinical outcome in patients with congestive heart failure (CHF). The adenosine monophosphate deaminase locus (AMPD1) was selected for study. We hypothesized that inheritance of the mutant AMPD1 allele is associated with increased probability of survival without cardiac transplantation in patients with CHF.
Methods and Results—AMPD1 genotype was determined
in 132 patients with advanced CHF and 91 control reference subjects by
use of a polymerase chain reaction–based, allele-specific
oligonucleotide detection assay. In patients with CHF,
those heterozygous (n=20) or homozygous (n=1) for the mutant AMPD1
allele (AMPD1 +/- or -/-, respectively) experienced a
significantly longer duration of heart failure symptoms before referral
for transplantation evaluation than CHF patients homozygous for the
wild-type allele (AMPD1 +/+; n=111; 7.6±6.5 versus 3.2±3.6 years;
P<0.001). The OR of surviving without cardiac
transplantation 
5 years after initial hospitalization for CHF
symptoms was 8.6 times greater (95% CI: 3.05, 23.87) in those patients
carrying 1 mutant AMPD1 allele than in those carrying 2 wild-type
AMPD1 +/+ alleles.
Conclusions—After the onset of CHF symptoms, the mutant AMPD1 allele is associated with prolonged probability of survival without cardiac transplantation. The mechanism by which the presence of the mutant AMPD1 allele may modify the clinical phenotype of heart failure remains to be determined.
Key Words: heart failure • genes • survival
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