ACE I/D polymorphism associated with abnormal atrial and atrioventricular conduction in lone atrial fibrillation and structural heart disease: implications for electrical remodeling.
BACKGROUND
The angiotensin-converting enzyme (ACE) gene contains a common polymorphism based on the insertion (I) or deletion (D) of a 287-bp intronic DNA fragment. The D allele is associated with higher ACE activity and thus higher angiotensin II levels. Angiotensin II stimulates cardiac fibrosis and conduction heterogeneity.


OBJECTIVE
The purpose of this study was to determine whether the ACE I/D polymorphism modulates cardiac electrophysiology.


METHODS
Three different cohorts of patients were studied: 69 patients with paroxysmal lone atrial fibrillation (AF), 151 patients with structural heart disease and no history of AF, and 161 healthy subjects without cardiovascular disease or AF. Patients taking drugs that affect cardiac conduction were excluded from the study. ECG parameters during sinus rhythm were compared among the ACE I/D genotypes.


RESULTS
The ACE I/D polymorphism was associated with the PR interval and heart block in the lone AF cohort. In multivariable linear regression models, the D allele was associated with longer PR interval in the lone AF and heart disease cohorts (12.0-ms and 7.1-ms increase per D allele, respectively). P-wave duration showed a similar trend, with increase in PR interval across ACE I/D genotypes in the lone AF and heart disease cohorts.


CONCLUSIONS
The ACE D allele is associated with electrical remodeling in patients with lone AF and in those with heart disease, but not in control subjects. ACE activity may play a role in cardiac remodeling after the development of AF and heart disease.
Watanabe
Hiroshi
H
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Kaiser
Daniel W
DW
Makino
Seiko
S
MacRae
Calum A
CA
Ellinor
Patrick T
PT
Wasserman
Brian S
BS
Kannankeril
Prince J
PJ
Donahue
Brian S
BS
Roden
Dan M
DM
Darbar
Dawood
D
D000328:Adult; D000804:Angiotensin II; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D001283:Atrioventricular Node / Q000294:innervation / Q000503:physiopathology*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006325:Heart Atria / Q000294:innervation / Q000503:physiopathology; D006327:Heart Block; D006331:Heart Diseases / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D020257:Ventricular Remodeling / Q000235:genetics
D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A