Renin-angiotensin system gene polymorphisms and atrial fibrillation: A regression approach for the detection of gene-gene interactions in a large hospitalized population

Chia Ti Tsai, Juey Jen Hwang, Fu Tien Chiang, Yi Chih Wang, Chuen Den Tseng, Yung Zu Tseng, Jiunn Lee Lin

Research output: Contribution to journalArticle

27 Citations (Scopus)


Objectives: To test the association between renin-angiotensin system gene variants and atrial fibrillation (AF) using a regression approach. Methods: A total of 1,236 consecutive patients (227 with AF and 1,009 with normal sinus rhythm as controls) were recruited. Angiotensin-converting enzyme (ACE) gene I/D polymorphism; T174M, M235T, G-6A, A-20C, G-152A and G-217A polymorphisms of the angiotensinogen (AGT) gene, and A1166C polymorphism of the angiotensin II type I receptor (AT1R) gene were genotyped. We used a regression approach based on a generalized linear model to evaluate haplotype effects and to detect gene-gene interactions by incorporating interaction terms in the model. Results: In single-locus analyses, no locus was associated with AF. After adjustment for AF risk factors, we found significant differences in the global AGT gene haplotype profile (the global score statistic = 30.364, p = 0.001) and individual haplotype frequencies between AF patients and controls. Furthermore, significant 2-way gene-gene interactions between ACE I/D polymorphism and AGT gene haplotypes and between AT1R A1166C polymorphism and AGT gene haplotypes, and 3-way interaction between ACE I/D, AT1R A1166C and AGT gene haplotypes were detected. Conclusions: These results are compatible with the concept of multilocus and multigene effects in determining the risk of complex diseases such as AF, which would be missed with conventional single-locus approaches.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
Issue number1
Publication statusPublished - Jul 1 2008
Externally publishedYes



  • Angiotensinogen
  • Atrial fibrillation
  • Haplotype
  • Multilocus
  • Regression
  • Renin-angiotensin system

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

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