Kolek Matthew J, Carlquist John F, Thaneemit-Chen Surai, Lazzeroni Laura C, Whiting Bryant M, Horne Benjamin D, Muhlestein Joseph B, Lavori Philip, Anderson Jeffrey L
Cardiovascular Department, LDS Hospital, Salt Lake City, UT 84143, USA.
J Card Fail. 2005 Dec;11(9):677-83. doi: 10.1016/j.cardfail.2005.06.437.
A common variant of the adenosine monophosphate deaminase (AMPD)-1 gene (C34T) results in enzymatic inactivity and may increase adenosine in cardiac muscle and confer cardioprotection through ischemic preconditioning.
We hypothesized that AMPD1 carriers with ischemic heart failure (HF) in the Beta-Blocker Evaluation of Survival Trial (BEST) might have a relative survival advantage. Patients (n = 1038, 20% black) with ischemic (58%) and nonischemic (42%) HF were followed for an average of 2.0 years for cardiovascular mortality. DNA was purified from blood using phenol/chloroform. Genotyping was performed by polymerase chain reaction with 5' exonuclease chemistry. Differences in survival were assessed by comparing Kaplan-Meier curves with the log-rank test. Genotype frequencies differed by ethnicity (P < .001) but not by disease etiology. AMPD1 genotype did not significantly modify survival in the entire study population (hazard ratio [HR] = 0.91, 95% CI = 0.61-1.37), among ischemics (HR = 0.73, CI = 0.44-1.22, P = .23), or ischemic non-blacks (HR = 0.74, CI = 0.44-1.24, P = .25). Genotype did not modify the effect of bucindolol on mortality.
Results of this study failed to confirm a reported survival benefit among HF patients carrying the AMPD1 T-allele. However, further studies in larger, more homogeneous populations should explore the possibility of a modest survival advantage for patients with ischemic HF.
腺苷单磷酸脱氨酶（AMPD）-1基因的一种常见变体（C34T）会导致酶失活，并可能增加心肌中的腺苷，通过缺血预处理赋予心脏保护作用。
我们假设在β受体阻滞剂对生存影响的评估试验（BEST）中，携带缺血性心力衰竭（HF）的AMPD1基因携带者可能具有相对生存优势。对1038例患者（20%为黑人）进行了平均2.0年的随访，观察心血管死亡率，其中缺血性HF患者占58%，非缺血性HF患者占42%。使用苯酚/氯仿从血液中纯化DNA。采用5'核酸外切酶化学的聚合酶链反应进行基因分型。通过对数秩检验比较Kaplan-Meier曲线来评估生存差异。基因型频率因种族而异（P <.001），但不因疾病病因而异。在整个研究人群中，AMPD1基因型并未显著改变生存率（风险比[HR]=0.91，95%可信区间[CI]=0.61 - 1.37），在缺血性患者中（HR = 0.73，CI = 0.44 - 1.22，P =.23），或缺血性非黑人患者中（HR = 0.74，CI = 0.44 - 1.24，P =.25）。基因型并未改变布辛多洛对死亡率的影响。
本研究结果未能证实报道的携带AMPD1 T等位基因的HF患者的生存获益。然而，在更大、更同质的人群中进行进一步研究应探索缺血性HF患者存在适度生存优势的可能性。
