ACE Insertion/Deletion, But Not-240A>T Polymorphism, Modulates the Severity in Heart Failure

Objective: ACE gene is reported to be a candidate gene in heart failure. The insertion/deletion (I/D) polymorphism has been observed to be a predictor of mortality in this disease, but no data are available concerning the role of ACE -240A>T polymorphism. In this study, we investigated the role of ACE I/D and -240A>T polymorphisms in influencing both severity and clinical outcomes in patients with heart failure, according to New York Heart Association (NYHA) class. Patients: We studied 323 patients with heart failure (258 men/65 women; age, 70.8 +/- 11.5 years) followed-up for 11.9 6.6 months. Results: The ACE D and -240T allele frequency significantly increased according to the NYHA functional class (P = 0.0002 and P < 0.0001, respectively). No significant difference in ACE polymorphism genotype distribution and allele frequency according to N-terminal pro-brain natriuretic peptide tertiles was observed. At multinomial regression analysis, ACE D but not -240T allele has been evidenced to be a significant and independent predictor of severity for both NYHA III and IV classes (P = 0.01 and P = 0.004, respectively). The ACE D allele prevalence was higher, even if not significantly in both death and rehospitalization groups in comparison with survivors and nonrehospitalized (P = 0.6 and P = 0.9, respectively). No difference in -240T allele frequency has been observed for the ACE -240A>T polymorphism, in relation to both death and rehospitalization (P = 0.1 and P = 0.6, respectively). Conclusions: This study suggests that ACE I/D polymorphism might represent a predisposing factor to severe heart failure, independently of well-known prognostic markers.