Azzam Naiel, Zafrir Barak, Fares Fuad, Smith Yoav, Salman Nabeeh, Nevzorov Roman, Amir Offer
Department of Human Biology, Faculty of Natural Sciences, University of Haifa, Haifa, Israel; Department of Molecular Genetics, Carmel Medical Center, Haifa, Israel.
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.
Nitric Oxide. 2015 May 1;47:91-6. doi: 10.1016/j.niox.2015.04.004. Epub 2015 Apr 23.
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).
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.
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.
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.
内皮型一氧化氮合酶（eNOS）基因单核苷酸多态性G894T与血栓性血管疾病相关。然而，其功能意义存在争议，且关于其对心力衰竭（HF）影响的数据较少。
我们研究了215例慢性收缩性HF患者。采用聚合酶链反应（PCR）和DNA测序分析eNOS基因G894T多态性的DNA。相对于TT和GT变体，对纯合G等位基因G894T变体（GG）进行临床特征评估和与2年死亡率相关因素的分析。
eNOS G894T等位基因的基因型分布为：GG 135例患者（63%），TT/GT 80例（37%）。GG变体的2年死亡率（48%）显著高于TT/GT联合组（32%）。使用硝酸盐与2年死亡率增加相关（风险比[HR] 2.0，95%置信区间[CI] 1.28 - 3.17；p = 0.003），与未使用硝酸盐的TT/GT组（34%）相比，在使用硝酸盐的GG组中最为显著（73.5%）；HR 2.75，95% CI 1.57 - 4.79，P < 0.001。
eNOS G894T多态性的G等位基因纯合性与收缩性HF患者较差的生存率相关，尤其是在使用硝酸盐治疗的患者中。与血栓性血管疾病相比，ENOS多态性在HF中可能导致不同的机制相互作用，提示一氧化氮（NO）的过度表达可能与收缩性HF中的有害作用相关。
