Relation between AT1R gene polymorphism and long-term outcome in patients with heart failure.
OBJECTIVE
Angiotensin II plays a key role in the pathophysiology of heart failure (HF). This study examined the angiotensin II type 1 receptor (AT1R) polymorphism in patients with systolic HF and its relation to clinical manifestations and patient outcome.


METHODS
We genotyped 134 patients with HF and reduced systolic function for the AT1R A1166C genotype using polymerase chain reaction and restriction fragment length polymorphism. We analyzed the relationship between the AT1R A1166C polymorphism and clinical, electrocardiographic, echocardiographic and laboratory parameters in patients with ischemic and non-ischemic etiology and examined the relation between the AT1R genotype and long-term (30 months) patient survival.


RESULTS
In HF patients, frequency of the AT1R 1166C allele and specifically the CC genotype was similar to the general population, but associated with an ischemic and not a non-ischemic etiology (p = 0.02). The CC genotype was associated with more advanced disease and more severe abnormalities of renal function (p = 0.008). Survival analysis showed that AT1R CC homozygous patients had significantly higher mortality (p = 0.008; adjusted odds ratio for mortality 6.35, 95% confidence interval 1.49-11.21, p = 0.01).


CONCLUSIONS
The CC AT1R genotype was associated with poor prognostic markers and increased mortality. The findings support the principle of genome-based therapies in the future treatment of HF patients.
Amir
Offer
O
Heart Failure Center, Department of Cardiovascular Medicine, Lady Davis Carmel and Lin Medical Centers, Haifa, Israel.
Amir
Ruthie E
RE
Paz
Hagar
H
Attias
Eric
E
Sagiv
Michael
M
Lewis
Basil S
BS
D000368:Aged; D005260:Female; D006239:Haplotypes; D006333:Heart Failure / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics
D044140:Receptor, Angiotensin, Type 1