Details

Autor(en) / Beteiligte

• Roberts, Jason D., MD
• Dewland, Thomas A., MD
• Glidden, David V., PhD
• Hoffman, Thomas J., PhD
• Arking, Dan E., PhD
• Chen, Lin Y., MD, MS
• Psaty, Bruce M., MD, PhD
• Olgin, Jeffrey E., MD
• Alonso, Alvaro, MD, PhD
• Heckbert, Susan R., MD, PhD
• Marcus, Gregory M., MD, MAS

Titel

Impact of Genetic Variants on the Upstream Efficacy of Renin-Angiotensin System Inhibitors for the Prevention of Atrial Fibrillation

Ist Teil von

• The American heart journal, 2016-05, Vol.175, p.9-17

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Background Renin angiotensin system (RAS) inhibition via ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) may reduce the risk of developing atrial fibrillation (AF) in certain populations, but the evidence is conflicting. Recent genome wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with AF, potentially identifying clinically relevant subtypes of the disease. We sought to investigate the impact of carrier status of 9 AF-associated SNPs on the efficacy of RAS inhibition for the primary prevention of AF. Methods We performed SNP-RAS inhibitor interaction testing with unadjusted and adjusted Cox proportional hazards models using a discovery (Cardiovascular Health Study [CHS]) and a replication (Atherosclerosis Risk in Communities [ARIC]) cohort. Additive genetic models were employed for the SNP analyses and two-tailed p-values < 0.05 were considered statistically significant Results Among 2796 CHS participants. none of the 9 a priori identified candidate SNPs exhibited a significant SNP-drug interaction. Two of the 9 SNPs, rs2106261 (16q22) and rs6666258 (1q21), revealed interaction relationships that neared statistical significance (with point estimates in the same direction for ACEi only and ARB only analyses), but neither association could be replicated among 8604 participants in ARIC. Conclusions Our study failed to identify AF-associated SNP genetic sub-types of AF that derive increased benefit from upstream RAS inhibition for AF prevention. Future studies should continue to investigate the impact of genotype on the response to AF treatment strategies in an effort to develop personalized approaches to therapy and prevention.