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

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302 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

Keywords

  • Angiotensin
  • Arrhythmia
  • Fibrillation
  • Genetics
  • Renin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Tsai, C. T., Lai, L. P., Lin, J. L., Chiang, F. T., Hwang, J. J., Ritchie, M. D., Moore, J. H., Hsu, K. L., Tseng, C. D., Liau, C. S., & 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