Background: The endothelial nitric oxide synthase (eNOS) gene single nucleotide polymorphism G894T was repeatedly shown to be associated with thrombotic vascular diseases. However, its functional significance is controversial and data is scarce concerning the influence of this polymorphism on the clinical outcome 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), relatively 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 [65 patients (48%)] than the combined TT/GT group [26 patients (32%)]; hazard ratio (HR) for mortality associated with GG genotype 1.6 [95% confidence interval (CI) 1.01-2.52; p=0.04]. 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. We therefore suggest that genetic variations of the eNOS polymorphism may result in different mechanistic interactions in HF than in thrombotic vascular diseases, and that overexpression of NO (either endogenously or exogenously) may be associated with deleterious effects in systolic HF patients.
