A common variant of the AMPD1 gene predicts improved cardiovascular survival in patients with coronary artery disease
A common variant of the AMPD1 gene predicts improved cardiovascular survival in patients with coronary artery disease
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DOI：
10.1016/s0735-1097(00)00850-0
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发表时间：
2000-10-01
影响因子：
24
通讯作者：
Pearson, RR
中科院分区：
文献类型：
--
作者：
Anderson, JL;Habashi, J;Pearson, RR
目的探讨一种常见的AMPD 1基因变异是否与冠心病患者心血管存活率的提高有关。一个常见的，无意义的，点变异的AMPD 1基因（C34 T）的结果在酶的活性，并已与延长的生存在heartfailure.METHODS收集血液从367例接受冠状动脉造影。通过聚合酶链反应扩增和限制性内切酶消化进行基因分型，产生等位基因特异性片段。冠状动脉疾病定义为大于或等于1支冠状动脉的狭窄大于或等于70%。对患者进行了长达4.8年的前瞻性随访。生存统计比较杂（+/-）或纯合子（-/-）携带者与noncarrier.Results患者66 +/- 10岁; 79%是男性; 22.6%是杂合子和1.9%纯合子的变异AMPD 1（-）等位基因。在平均3.5 ± 1.0年期间，52例患者（14.2%）死亡，37例（10.1%）死于CV原因。AMPD 1（-）等位基因携带者的心血管死亡率为4.4%（4/90），而非携带者为11.9%（33/277）（p = 0.046）。在多变量回归分析中，只有年龄（风险比，1.11/年，p < 0.001）和AMPD 1（-）携带（风险比，0.36，p = 0.053）是CV死亡率的独立预测因素。结论：在血管造影证实的CAD患者中，AMPD 1基因的常见变异体携带与CV生存率的改善相关。功能障碍的AMPD 1（-）等位基因可能导致缺血事件期间心脏腺苷增加和心脏保护增加。腺苷一磷酸脱氨酶-l基因分型在冠心病的预后，机制和治疗的见解应进一步探讨。（J Am Coil Cardiol 2000;36：1248-52）（C）2000年由美国心脏病学会发布。
OBJECTIVE We tested whether a common AMPD1 gene variant is associated with improved cardiovascular (CV) survival in patients with coronary artery disease (CAD).BACKGROUND Reduced activity of adenosine monophosphate deaminase (AMPD) may increase production of adenosine, a cardioprotective agent. A common, nonsense, point variant of the AMPD1 gene (C34T) results in enzymatic inactivity and has been associated with prolonged survival in heart failure.METHODS Blood was collected from 367 patients undergoing coronary angiography. Genotyping was done by polymerase chain reaction amplification and restriction enzyme digestion, resulting in allele-specific fragments. Coronary artery disease was defined as greater than or equal to 70% stenosis pf greater than or equal to 1 coronary artery. Patients were followed prospectively for up to 4.8 years. Survival statistics compared hetero- (+/-) or homozygotic (-/-) carriers with noncarriers.RESULTS Patients were 66 +/- 10 years old; 79% were men; 22.6% were heterozygous and 1.9% homozygous for the variant AMPD1(-) allele. During a mean of 3.5 +/- 1.0 years, 52 patients (14.2%) died, 37 (10.1%) of CV causes. Cardiovascular mortality was 4.4% (4/90) in AMPD1(-) allele carriers compared with 11.9% (33/277) in noncarriers (p = 0.046). In multiple variable regression analysis, only age (hazard ratio, 1.11/year, p < 0.001) and AMPD1(-) carriage (hazard ratio, 0.36, p = 0.053) were independent predictors of CV mortality.CONCLUSIONS Carriage of a common variant of the AMPD1 gene was associated with improved CV survival in patients with angiographically documented CAD. The dysfunctional AMPD1(-) allele may lead to increased cardiac adenosine and increased cardioprotection during ischemic events. Adenosine monophosphate deaminase-l genotyping should be further explored in CAD for prognostic, mechanistic and therapeutic insights. (J Am Coil Cardiol 2000;36: 1248-52) (C) 2000 by the American College of Cardiology.