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ACE Insertion/Deletion, But Not −240A>T Polymorphism, Modulates the Severity in Heart Failure
  1. Cinzia Fatini, MD, PhD,
  2. Elena Sticchi, BS,
  3. Rossella Marcucci, MD, PhD,
  4. Abdihakim Abdullahi Said, BS,
  5. Stefano Del Pace, MD,
  6. Valerio Verdiani, MD,
  7. Carlo Nozzoli, MD,
  8. Gian Franco Gensini, MD,
  9. Rosanna Abbate, MD
  1. From the *Department of Medical and Surgical Critical Care, Thrombosis Centre and Centre for the Study at Molecular and Clinical Level of Chronic, Degenerative and Neoplastic Diseases to Develop Novel Therapies, University of Florence, Italy; †Fondazione Don Carlo Gnocchi, ONLUS, S.Maria degli Ulivi- IRCCS, Firenze.
  1. All authors meet criteria for authorship and will sign a statement attesting authorship, disclosing all potential conflicts of interest, and releasing the copyright should the manuscript be acceptable for publication.
  2. Reprints: Cinzia Fatini, MD, PhD, Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. E-mail: cinzia.fatini{at}unifi.it.

Abstract

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.

Key Words
  • ACE I/D and −240A>T gene polymorphisms
  • NYHA functional class
  • heart failure

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