Author + information
- Sen Matsumoto,
- Yasuhiko Sakata,
- Daisaku Nakatani,
- Shinichiro Suna,
- Masaya Usami,
- Masahiko Hara,
- Tetsuhisa Kitamura,
- Hiroshi Sato,
- Masatsugu Hori,
- Shinsuke Nanto and
- Issei Komuro
Although beta adrenergic receptor (ADRB) gene polymorphisms may modulate cardiac function, their effects on prognosis are still controversial. The aim of this study is to investigate the prognostic impacts of ADRB gene polymorphisms in the secondary prevention settings of acute myocardial infarction (AMI).
We genotyped of ADRB1, ADRB2, and ADRB3 gene polymorphisms (ADRB1: Arg389Gly, Ser49Gly, ADRB2: Arg16Gly, Gln27Glu, Thr164Ile, Arg–19Cys, and ADRB3: Trp64Arg) in 3,253 AMI survivors registered in the Osaka Acute Coronary Insufficiency Study between 1998 and 2008. The prognostic impact of these polymorphisms and their combination, which was identified by principle components analysis (PCA), were examined by multivariate Cox regression analysis. Their pharmacogenetic interactions with β–blockers, renin angiotensin system (RAS) inhibitors and statins were also examined. The endpoints were all–cause death and a composite of death and heart failure requiring hospitalization (HF).
During the median follow–up period of 1,756 days, there were 231 deaths and 193 HF. There was no significant association between any single polymorphism and endpoints. However, the combination of ADRB1 389Arg/Arg, ADRB1 49Ser/Gly or 49Gly/Gly, ADRB2 27Gln/Gln and ADRB2 −19Cys/Cys was significantly associated with an increased risk of all–cause death (HR 1.49; 95%CI: 1.03–2.15, p=0.033) and the composite endpoint (HR 1.35; 95%CI: 1.02–1.80, p=0.039). Notably, analysis of pharmacogenetic interaction revealed that no medications investigated had beneficial impact on the risk haplotype. Moreover, it was shown that β–blockers might have adverse prognostic impacts on the risk haplotype (P for interaction: 0.15 and 0.07 for all–cause death and the composite endpoint, respectively).
Not any single, but a combination of the ADRB gene polymorphisms affected prognosis in post–AMI patients. Importantly, β–blockers might have adverse effects in patients with the risk haplotype, although further study is warranted to confirm the results.
Special Session North, Room 120
Monday, March 11, 2013, 11:00 a.m.–11:15 a.m.
Session Title: Young Investigator Awards Competition: Cardiovascular Health Outcomes and Population Genetics
Abstract Category: Cardiovascular Health Outcomes and Population Genetics
Presentation Number: 409–5
- 2013 American College of Cardiology Foundation