Lone and secondary nonvalvular atrial fibrillation: role of a genetic susceptibility.
BACKGROUND
An involvement of the renin angiotensin system in atrial fibrillation (AF) has been hypothesized, and ACE DD genotype has been suggested to influence the predisposition to AF. The aim of this study was to investigate the role of the ACE I/D polymorphism in relation to the different clinical forms of AF, lone and secondary nonvalvular atrial fibrillation (NVAF).


METHODS
510 consecutive patients with documented NVAF (106 patients had lone, and 404 secondary NVAF), and 520 controls with a negative history of cardiovascular disease have been studied.


RESULTS
A significant difference in allele frequency between lone and secondary NVAF (p=0.002) has been found. The ACE D allele was associated with the predisposition to lone NVAF under a dominant, recessive and additive model, both at univariate and multivariate analysis, after adjustment for age and gender (multivariate analysis: dominant OR=2.87, p=0.02; recessive OR=2.01, p=0.003; additive OR=4.47, p<0.0001). ACE D allele was significantly associated with secondary NVAF at both univariate and multivariate analysis under a recessive and additive, but not dominant, model (multivariate analysis: recessive OR=1.89, p=0.001; additive OR=2.50, p<0.0001).


CONCLUSIONS
This study highlights the role of ACE gene in predisposing to both lone and secondary NVAF, further contributing to penetrate the genetic mechanisms responsible for this complex disease. The clinical relevance of our results may be related to the possible characterization of subjects predisposed to NVAF in the absence of traditional risk factors, and to the use of ACE-inhibitors therapy able to improve the arrhythmogenic substrate.
Fatini
Cinzia
C
Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Viale Morgagni 85, 50134 Florence, Italy. cinziafatini@hotmail.com
Sticchi
Elena
E
Gensini
Francesca
F
Gori
Anna Maria
AM
Marcucci
Rossella
R
Lenti
Meri
M
Michelucci
Antonio
A
Genuardi
Maurizio
M
Abbate
Rosanna
R
Gensini
Gian Franco
GF
D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors
C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A