Impact of synergistic polymorphisms in adrenergic receptor-related genes and cardiovascular events in patients with dilated cardiomyopathy.
BACKGROUND
Sustained cardiac adrenergic stimulation has been implicated in the progression of cardiovascular events in patients with dilated cardiomyopathy (DCM). Our group hypothesized that a combination of polymorphisms that result in increased synaptic norepinephrine release and enhanced receptor function would predispose patients with DCM to cardiovascular events. The effect of polymorphisms in adrenergic receptor-related genes on cardiovascular event-free survival in patients with idiopathic DCM was evaluated.


RESULTS
Genotyping at 3 loci (ADRB1 Ser49Gly and Arg389Gly, and NET T-182C) was performed in 83 patients with DCM. Patients were followed prospectively to the endpoint of cardiovascular events (mean follow-up, 45 months). Cardiovascular events were defined as cardiac death and emergent hospitalization as a result of congestive heart failure, arrhythmia, and cerebrovascular events. Analyses were conducted based on the number of predicted risk genotypes a patient carried. The ADRB1 Ser49 allele carrier, ADRB1 Arg389 allele carrier, and NET-182CC genotype were defined as the predicted risk genotypes. Cardiovascular event-free survival was compared based on the number of predicted risk genotypes. Cardiovascular event-free survival was significantly better in patients with fewer than 3 predicted risk genotypes than in those with 3 predicted risk genotypes.


CONCLUSIONS
Genotyping at these 3 loci might be a useful approach for identification of patients with DCM at risk for cardiovascular events.
Department of Integrated Medicine and Informatics, Ehime University Graduate School of Medicine, Toon, Japan. aogimoto@m.ehime-u.ac.jp
Akiyoshi
A
Ogimoto
Hideki
H
Okayama
Takayuki
T
Nagai
Jun
J
Suzuki
Katsuji
K
Inoue
Kazuhisa
K
Nishimura
Yuji
Y
Shigematsu
Yasuharu
Y
Tabara
Tetsuro
T
Miki
Jitsuo
J
Higaki
D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D056426:Genetic Loci; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D015996:Survival Rate
C547787:ADRB1 protein, human; D009124:Muscle Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D018342:Receptors, Adrenergic, beta-1; C493227:SLC6A2 protein, human