RGD Reference Report - ACE I/D polymorphism associated with abnormal atrial and atrioventricular conduction in lone atrial fibrillation and structural heart disease: implications for electrical remodeling. - Rat Genome Database

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ACE I/D polymorphism associated with abnormal atrial and atrioventricular conduction in lone atrial fibrillation and structural heart disease: implications for electrical remodeling.

Authors: Watanabe, H  Kaiser, DW  Makino, S  MacRae, CA  Ellinor, PT  Wasserman, BS  Kannankeril, PJ  Donahue, BS  Roden, DM  Darbar, D 
Citation: Watanabe H, etal., Heart Rhythm. 2009 Sep;6(9):1327-32. doi: 10.1016/j.hrthm.2009.05.014. Epub 2009 May 15.
RGD ID: 8142351
Pubmed: PMID:19648063   (View Abstract at PubMed)
PMCID: PMC2740737   (View Article at PubMed Central)
DOI: DOI:10.1016/j.hrthm.2009.05.014   (Journal Full-text)

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. CONCLUSION: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
atrial fibrillation susceptibilityIAGP 8142351DNA:deletion:intron:IVS16+1464-1751del (human)RGD 
atrial fibrillation susceptibilityISOACE (Homo sapiens)8142351; 8142351DNA:deletion:intron:IVS16+1464-1751del (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Abnormal PR interval susceptibilityIAGP 8142351DNA:deletion:intron:IVS16+1464-1751del RGD 
Heart block susceptibilityIAGP 8142351DNA:deletion:intron:IVS16+1464-1751del RGD 
Prolonged PR interval  IAGP 8142351DNA:deletion:intron:IVS16+1464-1751delRGD 
Objects Annotated

Genes (Rattus norvegicus)
Ace  (angiotensin I converting enzyme)

Genes (Mus musculus)
Ace  (angiotensin I converting enzyme)

Genes (Homo sapiens)
ACE  (angiotensin I converting enzyme)


Additional Information