Renin-angiotensin system gene polymorphisms and atrial fibrillation: A regression approach for the detection of gene-gene interactions in a large hospitalized population
Journal
Cardiology
Journal Volume
111
Journal Issue
1
Pages
1-7
Date Issued
2008
Author(s)
Abstract
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. Copyright ? 2008 S. Karger AG.
SDGs
Other Subjects
aged; article; cardiac patient; female; gene frequency; gene interaction; gene locus; genetic polymorphism; genotype; haplotype; heart atrium fibrillation; human; major clinical study; male; priority journal; regression analysis; renin angiotensin aldosterone system; risk factor; scoring system; sinus rhythm; statistical model; Aged; Aged, 80 and over; Angiotensinogen; Atrial Fibrillation; Female; Haplotypes; Humans; Linear Models; Male; Middle Aged; Multifactorial Inheritance; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Receptor, Angiotensin, Type 1
Type
journal article