Abstract | BACKGROUND: Little evidence is available regarding the impact of genetic polymorphisms on the risk of stroke in patients with atrial fibrillation (AF). Angiotensin II plays a pathophysiologic role in prothrombotic atrial endocardial remodeling. OBJECTIVE: The purpose of this study was to investigate the effect of polymorphisms of renin-angiotensin system genes on the incidence of stroke in a prospective cohort of patients with AF. METHODS: A total of 712 AF patients were longitudinally followed-up for 10.3 ± 2.7 years. Eight polymorphisms of renin-angiotensin system genes were genotyped. RESULTS: Patients carrying the G-6 allele in the promoter of the angiotensinogen gene, which was associated with higher promoter activity, were more likely to develop stroke than were noncarriers (hazard ratio 2.54, 95% confidence interval [1.26-5.12], P = .009 after adjustment for CHADS2 score). G-6A polymorphism provides information additional to CHADS2 on stroke risk prediction (C-statistic 0.672 vs. 0.724, P = .039). In haplotype analysis, angiotensinogen gene promoter haplotypes containing -217G/-6G, which was associated with the highest promoter activity, were associated with an increased risk of stroke (P = .004). G-217/G-6 haplotype carriers were even more likely to develop stroke than were noncarriers (hazard ratio 2.78, 95% confidence interval 1.37-5.64, P = .003 after multivariable adjustment). In pharmacogenetic analysis, the increased risk of stroke in subjects carrying G-6 was eliminated by concomitant treatment with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (P = .012 for interaction). CONCLUSION:
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Authors | Chia-Ti Tsai, Sheng-Nan Chang, Shu-Hsuan Chang, Jen-Kuang Lee, Lian-Yu Lin, Cho-Kai Wu, Chih-Chieh Yu, Yi-Chih Wang, Chuen-Den Tseng, Ling-Ping Lai, Juey-Jen Hwang, Fu-Tien Chiang, Jiunn-Lee Lin |
Journal | Heart rhythm
(Heart Rhythm)
Vol. 11
Issue 8
Pg. 1384-90
(Aug 2014)
ISSN: 1556-3871 [Electronic] United States |
PMID | 24732371
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved. |
Chemical References |
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Topics |
- Aged
- Alleles
- Atrial Fibrillation
(complications, genetics, metabolism)
- DNA
(genetics)
- Female
- Follow-Up Studies
- Forecasting
- Genotype
- Humans
- Male
- Middle Aged
- Polymorphism, Genetic
- Prospective Studies
- Renin-Angiotensin System
(genetics)
- Risk Factors
- Stroke
(etiology, genetics, metabolism)
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