Endothelial nitric oxide synthase polymorphism and prognosis in systolic heart failure patients

Naiel Azzam, Barak Zafrir, Fuad Fares, Yoav Smith, Nabeeh Salman, Roman Nevzorov, Offer Amir

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)91-96
Number of pages6
JournalNitric Oxide - Biology and Chemistry
Volume47
DOIs
StatePublished - 16 May 2015

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

Keywords

  • Nitric oxide
  • Polymorphism
  • Systolic heart failure

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cancer Research
  • Clinical Biochemistry

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