title: Renin-angiotensin system gene polymorphisms and atrial fibrillation: a regression approach for the detection of gene-gene interactions in a large hospitalized population.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chia-Ti
authors.initials: CT
authors.lastname: Tsai
authors.forename: Juey-Jen
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Fu-Tien
authors.initials: FT
authors.lastname: Chiang
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Wang
authors.forename: Chuen-Den
authors.initials: CD
authors.lastname: Tseng
authors.forename: Yung-Zu
authors.initials: YZ
authors.lastname: Tseng
authors.forename: Jiunn-Lee
authors.initials: JL
authors.lastname: Lin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000235:genetics*; D001281:Atrial Fibrillation / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A