Relation of beta(2)-adrenoceptor haplotype to risk of death and heart transplantation in patients with heart failure.
Heart failure (HF) is characterized by neurohormonal activation of the sympathetic nervous and renin-angiotensin systems. Genetic polymorphisms in these systems could alter the prognosis in HF. We hypothesized the genetic polymorphisms in the sympathetic nervous and renin-angiotensin systems are associated with adverse outcomes, defined as death or heart transplantation in patients with HF. A total of 227 patients with HF were enrolled from a tertiary care clinic and followed for outcomes for < or =4 years. Eight polymorphisms in 6 genes were genotyped: beta(1)-adrenergic receptor (ADRB1, S49G, R389G), beta(2)-adrenergic receptor (ADRB2, G16R, Q27E), alpha(2c)-adrenergic receptor (ADRA2C, insertion/deletion 322-325), angiotensinogen (AGT, M235T), angiotensin receptor type 1 (AGTR1, 1166A>C), and angiotensin-converting enzyme (ACE, insertion/deletion in intron 16). Most patients were treated according to consensus guidelines. Male gender (hazard ratio 2.24, 95% confidence interval 1.27 to 3.94), higher New York Heart Association functional class (hazard ratio 2.54, 95% confidence interval 1.84 to 3.52), and 2 copies of ADRB2 Arg16Gln27 haplotype (hazard ratio 1.91, 95% confidence interval 1.09 to 3.36) increased the risk of adverse outcomes. In contrast, a higher serum sodium level (hazard ratio 0.91, 95% confidence interval 0.86 to 0.97) and higher creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.98 to 0.99) decreased the risk of adverse outcomes. None of the other genotypes/haplotypes were associated with adverse outcomes. In conclusion, ADRB2 Arg16Gln27 haplotype may significantly increase the risk of adverse outcomes in patients with HF receiving contemporary HF pharmacotherapy.
Shin
Jaekyu
J
College of Pharmacy, Gainesville, Florida, USA.
Lobmeyer
Maximilian T
MT
Gong
Yan
Y
Zineh
Issam
I
Langaee
Taimour Y
TY
Yarandi
Hossein
H
Schofield
Richard S
RS
Aranda
Juan M
JM
Hill
James A
JA
Pauly
Daniel F
DF
Johnson
Julie A
JA
D004247:DNA / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006239:Haplotypes; D006333:Heart Failure / Q000235:genetics / Q000401:mortality / Q000601:surgery; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate
D018343:Receptors, Adrenergic, beta-2; D004247:DNA