Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation

Chia Ti Tsai, Ling Ping Lai, Jiunn Lee Lin, Fu Tien Chiang, Juey Jen Hwang, Marylyn D. Ritchie, Jason H. Moore, Kuan Lih Hsu, Chuen Den Tseng, Chiau Suong Liau, Yung Zu Tseng

Research output: Contribution to journalArticle

299 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1640-1646
Number of pages7
JournalCirculation
Volume109
Issue number13
DOIs
Publication statusPublished - Apr 6 2004
Externally publishedYes

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Renin-Angiotensin System
Atrial Fibrillation
Genes
Angiotensinogen
Genotype
Haplotypes
Multifactor Dimensionality Reduction
Angiotensin I
Heart Valve Diseases
Angiotensin Receptors
Insertional Mutagenesis
Linkage Disequilibrium
Gene Deletion
Left Ventricular Dysfunction
Angiotensin-Converting Enzyme Inhibitors
Angiotensin II
Case-Control Studies
Alleles
Odds Ratio
Clinical Trials

Keywords

  • Angiotensin
  • Arrhythmia
  • Fibrillation
  • Genetics
  • Renin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Tsai, C. T., Lai, L. P., Lin, J. L., Chiang, F. T., Hwang, J. J., Ritchie, M. D., ... Tseng, Y. Z. (2004). Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation. Circulation, 109(13), 1640-1646. https://doi.org/10.1161/01.CIR.0000124487.36586.26

Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation. / Tsai, Chia Ti; Lai, Ling Ping; Lin, Jiunn Lee; Chiang, Fu Tien; Hwang, Juey Jen; Ritchie, Marylyn D.; Moore, Jason H.; Hsu, Kuan Lih; Tseng, Chuen Den; Liau, Chiau Suong; Tseng, Yung Zu.

In: Circulation, Vol. 109, No. 13, 06.04.2004, p. 1640-1646.

Research output: Contribution to journalArticle

Tsai, CT, Lai, LP, Lin, JL, Chiang, FT, Hwang, JJ, Ritchie, MD, Moore, JH, Hsu, KL, Tseng, CD, Liau, CS & Tseng, YZ 2004, 'Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation', Circulation, vol. 109, no. 13, pp. 1640-1646. https://doi.org/10.1161/01.CIR.0000124487.36586.26
Tsai, Chia Ti ; Lai, Ling Ping ; Lin, Jiunn Lee ; Chiang, Fu Tien ; Hwang, Juey Jen ; Ritchie, Marylyn D. ; Moore, Jason H. ; Hsu, Kuan Lih ; Tseng, Chuen Den ; Liau, Chiau Suong ; Tseng, Yung Zu. / Renin-Angiotensin System Gene Polymorphisms and Atrial Fibrillation. In: Circulation. 2004 ; Vol. 109, No. 13. pp. 1640-1646.
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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.",
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AU - Hwang, Juey Jen

AU - Ritchie, Marylyn D.

AU - Moore, Jason H.

AU - Hsu, Kuan Lih

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N2 - 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.

AB - 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.

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