Evaluation of AMPD1 C34T genotype as a predictor of mortality in heart failure and post–myocardial infarction patients

Abstract

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. 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. 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). This study suggests that AMPD1 C34T genotype is not a predictor of survival in heart disease patients, except possibly those with HxMI.