Endothelial nitric oxide synthase polymorphism and prognosis in systolic heart failure patients.
BACKGROUND
The endothelial nitric oxide synthase (eNOS) gene single nucleotide polymorphism G894T is associated with thrombotic vascular diseases. However, its functional significance is controversial and data are scarce concerning its influence in heart failure (HF).


METHODS
We studied 215 patients with chronic systolic HF. DNA was analyzed for eNOS gene G894T polymorphism using PCR and DNA sequencing. Evaluation of clinical characteristics and analysis of factors associated with 2-year mortality were performed for the homozygous G-allele G894T variant (GG), relative to the TT and GT variants.


RESULTS
The genotype distributions of eNOS G894T alleles were: GG 135 patients (63%) and TT/GT 80 (37%). Two-year mortality was significantly higher in the GG variant (48%) than the combined TT/GT group (32%). The usage of nitrates was associated with increased 2-year mortality (HR 2.0, 95% CI 1.28-3.17; p = 0.003), which was most significant in the GG group treated with nitrates (73.5%) in comparison to the TT/GT group not treated with nitrates (34%); HR 2.75, 95% CI 1.57-4.79, P < 0.001.


CONCLUSIONS
Homozygosity for the G allele of the eNOS G894T polymorphism was associated with worse survival in systolic HF patients, especially in those treated with nitrates. ENOS polymorphism may result in different mechanistic interactions in HF than in thrombotic vascular diseases, suggesting that overexpression of NO may be associated with deleterious effects in systolic HF.
Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel; Department of Molecular Genetics, Carmel Medical Center, Haifa, Israel.
Naiel
N
Azzam
Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, Haifa, Israel; Ruth and Bruce Rappaport School of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.
Barak
B
Zafrir
Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel; Department of Molecular Genetics, Carmel Medical Center, Haifa, Israel.
Fuad
F
Fares
Genomic Data Analysis Unit, Hadassah Medical School, Hebrew University of Jerusalem, Israel.
Yoav
Y
Smith
Department of Cardiovascular Medicine, Poriya Medical Center, Tiberius, Israel; Faculty of Medicine, Bar-Ilan University, Israel.
Nabeeh
N
Salman
Department of Cardiovascular Medicine, Poriya Medical Center, Tiberius, Israel; Faculty of Medicine, Bar-Ilan University, Israel.
Roman
R
Nevzorov
Department of Cardiovascular Medicine, Poriya Medical Center, Tiberius, Israel; Faculty of Medicine, Bar-Ilan University, Israel. Electronic address: oamir@poria.health.gov.il.
Offer
O
Amir
D000368:Aged; D005260:Female; D054143:Heart Failure, Systolic / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis
D052250:Nitric Oxide Synthase Type III
Nitric oxide; Polymorphism; Systolic heart failure