Evaluation of AMPD1 C34T genotype as a predictor of mortality in heart failure and post-myocardial infarction patients.
BACKGROUND
The AMPD1 gene C34T polymorphism has previously been associated with prolonged survival in small cohorts of heart failure (HF) and coronary artery disease patients. This study aimed to corroborate the association of the AMPD1 C34T polymorphism with survival in larger myocardial infarction (MI) and HF cohorts.


METHODS
Genotypes were obtained for 935 post-MI (PMI) and 433 patients with established HF, with median follow-up times of 5.4 and 3.1 years, respectively. At admission, cardiac function was assessed by nuclear ventriculography (PMI) and echocardiography (HF) and plasma cardiac neurohormones were assayed.


RESULTS
Differences in mortality by AMPD1 genotype did not achieve significance, either for the overall HF (P = .07) or the overall PMI group (P = .28), but AMPD1 genotype predicted mortality in patients of both cohorts with a history of MI (HxMI). In contrast to previous studies, the mutant T allele was associated with poorer outcome. Mortality in HF HxMI patients was significantly different between genotype groups (n = 144, mortality CC 56.5%, CT/TT 77.8%, P = .027), but not in patients without HxMI. In PMI patients, the association of genotype with survival in the HxMI subgroup trended toward significance (n = 147, mortality CC 29.8%, CT/TT 45.5%, P = .093). Multivariate analysis of combined PMI and HF cohorts showed that HxMI patients with CT/TT genotype were at greater risk than all other groups (P < .001).


CONCLUSIONS
This study suggests that AMPD1 C34T genotype is not a predictor of survival in heart disease patients, except possibly those with HxMI.
Collins
Richard P
RP
Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand.
Palmer
Barry R
BR
Pilbrow
Anna P
AP
Frampton
Chris M
CM
Troughton
Richard W
RW
Yandle
Tim G
TG
Skelton
Lorraine
L
Richards
A Mark
AM
Cameron
Vicky A
VA
D000659:AMP Deaminase / Q000235:genetics*; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D019332:Endothelin-1 / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000235:genetics* / Q000401:mortality*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012189:Retrospective Studies
D019332:Endothelin-1; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D000659:AMP Deaminase; D009638:Norepinephrine; D004837:Epinephrine