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.
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.
Authors: Arthur M Feldman; Lilin She; Dennis M McNamara; Douglas L Mann; Michael R Bristow; Alan S Maisel; Daniel R Wagner; Bert Andersson; Luigi Chiariello; Christopher S Hayward; Paul Hendry; John D Parker; Normand Racine; Craig H Selzman; Michele Senni; Janina Stepinska; Marian Zembala; Jean Rouleau; Eric J Velazquez; Kerry L Lee Journal: Cardiology Date: 2015-01-13 Impact factor: 1.869
Authors: Bart P Ramakers; Niels P Riksen; Petra van den Broek; Barbara Franke; Wilbert H M Peters; Johannes G van der Hoeven; Paul Smits; Peter Pickkers Journal: Crit Care Date: 2011-01-06 Impact factor: 9.097
Authors: Ryszard T Smolenski; Iwona Rybakowska; Jacek Turyn; Paweł Romaszko; Magdalena Zabielska; Anne Taegtmeyer; Ewa M Słomińska; Krystian K Kaletha; Paul J R Barton Journal: Cardiovasc Drugs Ther Date: 2014-04 Impact factor: 3.727
Authors: Trevor Simard; Richard Jung; Alisha Labinaz; Mohammad Ali Faraz; F Daniel Ramirez; Pietro Di Santo; Dylan Perry-Nguyen; Ian Pitcher; Pouya Motazedian; Chantal Gaudet; Rebecca Rochman; Jeffrey Marbach; Paul Boland; Kiran Sarathy; Saleh Alghofaili; Juan J Russo; Etienne Couture; Steven Promislow; Rob S Beanlands; Benjamin Hibbert Journal: J Am Heart Assoc Date: 2019-08-05 Impact factor: 5.501