A common variant of the AMPD1 gene predicts improved cardiovascular survival in patients with coronary artery disease.
J Am Coll Cardiol
; 36(4): 1248-52, 2000 Oct.
Article
em En
| MEDLINE
| ID: mdl-11028479
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
Códon sem Sentido
/
Doença das Coronárias
/
AMP Desaminase
Tipo de estudo:
Observational_studies
/
Prognostic_studies
Limite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Am Coll Cardiol
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos