Effect of the Asp298 variant of endothelial nitric oxide synthase on survival for patients with congestive heart failure
Effect of the Asp298 variant of endothelial nitric oxide synthase on survival for patients with congestive heart failure
复制标题
DOI：
10.1161/01.cir.0000060540.93836.aa
复制
发表时间：
2003-04-01
期刊：
影响因子：
37.8
通讯作者：
London, B
中科院分区：
文献类型：
--
作者：
McNamara, DM;Holubkov, R;London, B
背景-内皮型一氧化氮合酶（NOS 3）基因存在显著变异，可能影响心血管风险。NOS 3的Asp（298）变体在内皮细胞中具有较短的半衰期。鉴于一氧化氮在心力衰竭综合征中的重要性，我们评估了这种变异对收缩功能障碍人群无事件生存率的影响。（72%男性，49%缺血性;平均年龄，56 +/- 12岁）伴收缩功能障碍（左室射血分数≤ 0.45）入选心脏事件遗传风险评估（GRACE）研究。对NOS 3外显子7的多态性（第894位的G-T转换导致密码子298的Glu变为Asp氨基酸取代）进行基因分型，并前瞻性随访受试者至死亡或心脏移植终点。根据Asp（298）变异体的存在（第1组，n=266）或不存在（第2组，n=203）比较无事件生存期。Asp（298）变异患者的无事件生存率明显较差（第1组1/2/3年无事件生存率百分比=78/65/54;第2组=82/72/64，P=0.03）。在亚组分析中，Asp（298）变异的不良影响主要发生在非缺血性心肌病患者中（组1=82/73/63;组2=87/79/71，P=0.03），在缺血性心脏病患者中不明显（1组=75/59/47; 2组=74/62/54，P=0.71）.结论：对于收缩功能引起的心力衰竭患者，NOS 3的Asp（298）变异与无事件生存率较差相关，特别是在非缺血性心肌病患者中。
Background-Significant variation exists within the endothelial nitric oxide synthase (NOS3) gene that may influence cardiovascular risk. The Asp(298) variant of NOS3 has a shorter half-life in endothelial cells. Given the importance of nitric oxide in the heart failure syndrome, we evaluated the effect of this variant on event-free survival in a population with systolic dysfunction.Methods and Results-Four hundred sixty-nine patients (72% male, 49% ischemic; mean age, 56 +/- 12 years) with systolic dysfunction (left ventricular ejection fraction less than or equal to0.45) were enrolled in a study of Genetic Risk Assessment of Cardiac Events (GRACE). The polymorphism in exon 7 of NOS3, a G-T transition at position 894 that results in a Glu to Asp amino acid substitution for codon 298, was genotyped and subjects were followed prospectively to the end point of death or heart transplantation. Event-free survival was compared on the basis of the presence (group 1, n=266) or absence (group 2, n=203) of the Asp(298) variant. Event-free survival was significantly poorer in patients with the Asp(298) variant (percent event-free survival group 1 at 1/2/3 years=78/65/54; group 2=82/72/64, P=0.03). In subset analysis, the adverse impact of the Asp(298) variant was primarily in patients with nonischemic cardiomyopathy (group 1=82/73/63; group 2=87/79/71, P=0.03) and was not apparent among patients with ischemic heart disease (group 1=75/59/47; group 2=74/62/54, P=0.71).Conclusions-For patients with heart failure caused by systolic function, the Asp(298) variant of NOS3 is associated with poorer event-free survival, particularly in patients with nonischemic cardiomyopathy.