Renin-angiotensin system gene polymorphisms predict the risk of stroke in patients with atrial fibrillation

A 10-year prospective follow-up study

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

Research output: Contribution to journalReview article

4 Citations (Scopus)

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 In addition to the CHADS2 score, angiotensinogen gene polymorphisms may be considered an additional genetic predictor of stroke in patients with AF. Genotyping of the angiotensinogen gene is helpful to determine which AF patients may benefit from treatment with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker.

Original languageEnglish
Pages (from-to)1384-1390
Number of pages7
JournalHeart Rhythm
Volume11
Issue number8
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

antineoplaston A10
Renin-Angiotensin System
Atrial Fibrillation
Stroke
Angiotensinogen
Genes
Haplotypes
Angiotensin Receptor Antagonists
Angiotensin-Converting Enzyme Inhibitors
Atrial Remodeling
Confidence Intervals
Genetic Polymorphisms
Angiotensin II
Alleles
Incidence
Therapeutics

Keywords

  • Atrial fibrillation
  • Pharmacogenetics
  • Polymorphisms
  • Prospective
  • Renin-angiotensin system
  • Stroke

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Renin-angiotensin system gene polymorphisms predict the risk of stroke in patients with atrial fibrillation : A 10-year prospective follow-up study. / Tsai, Chia Ti; Chang, Sheng Nan; Chang, Shu Hsuan; Lee, Jen Kuang; Lin, Lian Yu; Wu, Cho Kai; Yu, Chih Chieh; Wang, Yi Chih; Tseng, Chuen Den; Lai, Ling Ping; Hwang, Juey Jen; Chiang, Fu Tien; Lin, Jiunn Lee.

In: Heart Rhythm, Vol. 11, No. 8, 01.01.2014, p. 1384-1390.

Research output: Contribution to journalReview article

Tsai, CT, Chang, SN, Chang, SH, Lee, JK, Lin, LY, Wu, CK, Yu, CC, Wang, YC, Tseng, CD, Lai, LP, Hwang, JJ, Chiang, FT & Lin, JL 2014, 'Renin-angiotensin system gene polymorphisms predict the risk of stroke in patients with atrial fibrillation: A 10-year prospective follow-up study', Heart Rhythm, vol. 11, no. 8, pp. 1384-1390. https://doi.org/10.1016/j.hrthm.2014.04.014
Tsai, Chia Ti ; Chang, Sheng Nan ; Chang, Shu Hsuan ; Lee, Jen Kuang ; Lin, Lian Yu ; Wu, Cho Kai ; Yu, Chih Chieh ; Wang, Yi Chih ; Tseng, Chuen Den ; Lai, Ling Ping ; Hwang, Juey Jen ; Chiang, Fu Tien ; Lin, Jiunn Lee. / Renin-angiotensin system gene polymorphisms predict the risk of stroke in patients with atrial fibrillation : A 10-year prospective follow-up study. In: Heart Rhythm. 2014 ; Vol. 11, No. 8. pp. 1384-1390.
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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 In addition to the CHADS2 score, angiotensinogen gene polymorphisms may be considered an additional genetic predictor of stroke in patients with AF. Genotyping of the angiotensinogen gene is helpful to determine which AF patients may benefit from treatment with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker.",
keywords = "Atrial fibrillation, Pharmacogenetics, Polymorphisms, Prospective, Renin-angiotensin system, Stroke, Atrial fibrillation, Pharmacogenetics, Polymorphisms, Prospective, Renin-angiotensin system, stroke",
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T1 - Renin-angiotensin system gene polymorphisms predict the risk of stroke in patients with atrial fibrillation

T2 - A 10-year prospective follow-up study

AU - Tsai, Chia Ti

AU - Chang, Sheng Nan

AU - Chang, Shu Hsuan

AU - Lee, Jen Kuang

AU - Lin, Lian Yu

AU - Wu, Cho Kai

AU - Yu, Chih Chieh

AU - Wang, Yi Chih

AU - Tseng, Chuen Den

AU - Lai, Ling Ping

AU - Hwang, Juey Jen

AU - Chiang, Fu Tien

AU - Lin, Jiunn Lee

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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 In addition to the CHADS2 score, angiotensinogen gene polymorphisms may be considered an additional genetic predictor of stroke in patients with AF. Genotyping of the angiotensinogen gene is helpful to determine which AF patients may benefit from treatment with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker.

AB - 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 In addition to the CHADS2 score, angiotensinogen gene polymorphisms may be considered an additional genetic predictor of stroke in patients with AF. Genotyping of the angiotensinogen gene is helpful to determine which AF patients may benefit from treatment with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker.

KW - Atrial fibrillation

KW - Pharmacogenetics

KW - Polymorphisms

KW - Prospective

KW - Renin-angiotensin system

KW - Stroke

KW - Atrial fibrillation

KW - Pharmacogenetics

KW - Polymorphisms

KW - Prospective

KW - Renin-angiotensin system

KW - stroke

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