Influence of ALDH2 Glu504Lys polymorphism on nitroglycerin response in chronic heart failure and involvement of Calcitonin Gene Related Peptide (CGRP)
Influence of ALDH2 Glu504Lys polymorphism on nitroglycerin response in chronic heart failure and involvement of Calcitonin Gene Related Peptide (CGRP)
复制标题
ALDH2 Glu504Lys 多态性对慢性心力衰竭硝酸甘油反应的影响以及降钙素基因相关肽 (CGRP) 的参与。
DOI：
10.5414/cp201635
复制
发表时间：
2012-10-01
影响因子：
0.8
通讯作者：
Li, Chuan-Chang
中科院分区：
文献类型：
--
作者：
Peng, Li-Ming;Chen, Xiao-Ping;Li, Chuan-Chang
目的
本研究旨在探讨神经肽降钙素基因相关肽（CGRP）是否参与慢性心力衰竭（CHF）患者的硝酸甘油（GTN）反应以及与线粒体乙醛脱氢酶-2（ALDH2）Glu504Lys（ALDH2 * 2）多态性的关系。
方法
这是一项2阶段、安慰剂对照临床研究。对49例稳定期CHF患者静脉滴注生理盐水和GTN（20 μ g/min），各2h。在基线、开始生理盐水输注和开始GTN治疗后10 min、30 min、1.0 h、1.5 h和2.0 h测量血压（BP）、心率（HR）和呼吸频率（RR）。49例患者分别在基线、开始输注生理盐水和GTN后2.0 h抽血测定血浆CGRP。评价患者的总体临床状态。在基线和开始输注生理盐水和GTN后2.0 h，由同一研究者采用Simpson双平面法（Pillip HP sonos 5500）进行2D超声心动图测量左心室射血分数（LVEF）、左心室舒张末期容积（LVEDV）、每搏输出量（SV）和心输出量（CO）。
结果
在GTN输注结束时，收缩压（SBP）、舒张压（DBP）和左心室舒张末期容积（LVEDV）降低，而左心室射血分数（LVEF）升高（分别为p <0.001）。生理盐水输注未显示血流动力学影响。在GTN输注结束时，ALDH 2 * 1/* 1纯合子患者的SBP（DSBP）绝对下降（p <0.001）和LVEF增加（p <0.001）的程度均高于ALDH 2 * 2等位基因携带者。GTN输注后血浆CGRP浓度明显升高（p <0.001），而生理盐水输注后无明显变化（p> 0.05）。血浆CGRP浓度的变化与LVEF的改善呈正相关（r = 0.400，p = 0.004），与SBP（r =-0.300，p = 0.036）和LVEDV（r =-0.290，p = 0.043）的变化呈负相关。
结论
ALDH2 * 2基因多态性与CHF患者CGRP对GTN反应的贡献相关。
OBJECTIVE
The aim of this study was to investigate whether the neuropeptide calcitonin gene related peptide (CGRP) contributes to nitroglycerin (GTN) response in patients with chronic heart failure (CHF) and the association with the mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys (ALDH2*2) polymorphism.
METHODS
This is a 2-period, placebo-controlled clinical study. An intravenous infusion of saline followed by GTN (20 μg/min), each for 2 hours, respectively, was given to 49 stable CHF patients. Blood pressure (BP), heart rate (HR) and respiratory rate (RR) were measured at baseline, at 10 min, 30 min, 1.0 h, 1.5 h, and 2.0 h after initiation of saline infusion and initiation of GTN therapy. Blood samples were drawn for the determination of plasma CGRP for 49 patients at baseline, and at 2.0 h after initiation of saline and GTN infusion, respectively. Global clinical status of the patients was evaluated. Left ventricular ejection (LVEF), left ventricular end-diastolic volume (LVEDV), stroke volume (SV) and cardiac output (CO) were measured with 2D echocardiography with Simpson's biplane method (Pillip HP sonos 5500) by the same investigator at baseline and at 2.0 h after initiation of saline and GTN infusion.
RESULTS
Systolic blood pressure (SBP), diastolic blood pressure (DBP), and left ventricular end-diastolic volume (LVEDV) were decreased, while left ventricular ejection fraction (LVEF) was increased at the end of GTN infusion (p < 0.001, respectively). Saline infusion showed no hemodynamic effects. At the end of GTN infusion, ALDH2*1/*1 homozygous patients showed higher degrees of both the absolute decrease in SBP (DSBP) (p < 0.001) and increase in LVEF (p < 0.001) than carriers of the ALDH2*2 allele. Mean plasma concentration of CGRP was increased after GTN infusion (p < 0.001), but not changed after saline infusion (p > 0.05). Changes in plasma concentration of CGRP correlated positively with the improvement in LVEF (r = 0.400, p = 0.004), while correlated negatively with changes in SBP (r = -0.300, p = 0.036) and LVEDV (r = -0.290, p = 0.043).
CONCLUSIONS
ALDH2*2 polymorphism is associated with contributions of CGRP to GTN response in CHF patients.