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.


METHODS
: 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.
Fatini
Cinzia
C
Department of Medical and Surgical Critical Care, Thrombosis Centre and Centre for the Study at Molecular and Clinical Level of Chronic, University of Florence, Italy. cinzia.fatini@unifi.it
Sticchi
Elena
E
Marcucci
Rossella
R
Said
Abdihakim Abdullahi
AA
Del Pace
Stefano
S
Verdiani
Valerio
V
Nozzoli
Carlo
C
Gensini
Gian Franco
GF
Abbate
Rosanna
R
D000328:Adult; D000368:Aged; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006333:Heart Failure / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D020097:Natriuretic Peptide, Brain / Q000032:analysis; D010446:Peptide Fragments / Q000032:analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic
D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D007703:Peptidyl-Dipeptidase A