Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation
Journal
Circulation
Journal Volume
109
Journal Issue
13
Pages
1640-1646
Date Issued
2004
Author(s)
Ritchie M.D.
Moore J.H.
Hsu K.-L.
Tseng C.-D.
Liau C.-S.
Tseng Y.-Z.
Abstract
Background - The activated local atrial renin-angiotensin system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation (AF). We hypothesized that RAS genes might be among the susceptibility genes of nonfamilial structural AF and conducted a genetic case-control study to demonstrate this. Methods and Results - A total of 250 patients with documented nonfamilial structural AF and 250 controls were selected. The controls were matched to cases on a 1-to-1 basis with regard to age, gender, presence of left ventricular dysfunction, and presence of significant valvular heart disease. The ACE gene insertion/deletion polymorphism, the T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen gene, and the A1166C polymorphism of the angiotensin II type I receptor gene were genotyped. In multilocus haplotype analysis, the angiotensinogen gene haplotype profile was significantly different between cases and controls (χ2=62.5, P=0.0002). In single-locus analysis, M235T, G-6A, and G-217A were significantly associated with AF. Frequencies of the M235, G-6, and G-217 alleles were significantly higher in cases than in controls (P=0.000, 0.005, and 0.002, respectively). The odds ratios for AF were 2.5 (95% CI 1.7 to 3.3) with M235/M235 plus M235/T235 genotype, 3.3 (95% CI 1.3 to 10.0) with G-6/G-6 genotype, and 2.0 (95% CI 1.3 to 2.5) with G-217/G-217 genotype. Furthermore, significant gene-gene interactions were detected by the multifactor-dimensionality reduction method and multilocus linkage disequilibrium tests. Conclusions - This study demonstrates the association of RAS gene polymorphisms with nonfamilial structural AF and may provide the rationale for clinical trials to investigate the use of ACE inhibitor or angiotensin II antagonist in the treatment of structural AF.
SDGs
Other Subjects
angiotensin 1 receptor; angiotensin antagonist; angiotensinogen; dipeptidyl carboxypeptidase inhibitor; adult; aged; article; controlled study; DNA polymorphism; female; gene deletion; gene frequency; gene insertion; gene interaction; gene linkage disequilibrium; gene locus; genetic susceptibility; genotype; haplotype; heart arrhythmia; heart atrium fibrillation; human; major clinical study; male; pathogenesis; priority journal; renin angiotensin aldosterone system; Aged; Aged, 80 and over; Angiotensinogen; Atrial Fibrillation; Epistasis, Genetic; Female; Gene Frequency; Genetic Predisposition to Disease; Haplotypes; Heart Atria; Heart Valve Diseases; Humans; Linkage Disequilibrium; Male; Middle Aged; Mutagenesis, Insertional; Promoter Regions (Genetics); Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Sequence Deletion; Taiwan
Type
journal article