Abstract 2514: Common Polymorphisms in the Angiotensinogen and ACE Genes: Risk of Atrial Fibrillation in the General Population
Aim: To study risk of atrial fibrillation in individuals with single nucleotide polymorphisms (SNPs) in the angiotensinogen and ACE genes involved in the renin-angiotensin activating system.
Methods: 9,257 individuals from the Danish general population were screened for five common SNPs: A-20C, G-6A, T174M and M235T in the angiotensinogen gene and the insertion/deletion polymorphism in the ACE gene. All participants included were in sinus-rhythm at baseline. Participants were followed until atrial fibrillation occurred or until the end of follow-up, whichever came first. We observed 537 incident events of atrial fibrillation.
Results: The M-genotype at the T174M locus was associated with an increased risk of atrial fibrillation for both heterozygotes and homozygotes (hazard ratios: 1.3 (1.1–1. 6) and 1.9 (1.1–3.4)). Women heterozygous for the two-site combination of A-20C and ACE insertion/ deletion had a risk of 1.7 (1.1–2.6) while those homozygous for both loci had a risk of 4.0 (1.7–9.4). Combining all five SNPs into a combined genotype identified two five-site combinations associated with an increased risk of 2.3 (1.4 –3.8) and 2.4 (1.1–5.1), respectively. In individuals with body mass index above 25 kg/m2, age above 70 years and with severe hypertension, T174M homozygosity was associated with a 10-years absolute risk of atrial fibrillation of 70%.
Conclusion: SNPs in the angiotensinogen and ACE genes are associated with up to a four-fold relative risk of atrial fibrillation, and up to a 70% 10-years absolute risk of atrial fibrillation in overweight, elderly persons with hypertension.