Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients
Apolipoprotein E4 polymorphism as a genetic predisposition to delirium in critically ill patients
复制标题
DOI：
10.1097/01.ccm.0000251925.18961.ca
复制
发表时间：
2007-01-01
影响因子：
8.8
通讯作者：
Laskowitz, Daniel T.
中科院分区：
文献类型：
--
作者：
Ely, E. Wesley;Girard, Timothy D.;Laskowitz, Daniel T.
客观，为检测载脂蛋白E（APOE）基因型与重症监护室谵妄持续时间之间的相关性，设计：前瞻性、观察性队列研究，地点：一家拥有541张床位的社区教学医院，患者：53名机械通气重症监护室患者。无.测量和主要结果.，作为正在进行的临床试验的一部分，所有患者均采用标准化镇静和呼吸机撤机方案进行管理，并采用重症监护病房（CAM-ICU）的混乱评估方法前瞻性评估谵妄。从入组时获得的全血样本中提取DNA，由对临床信息不知情的研究者使用聚合酶链反应和限制性内切酶消化确定APOE基因型。在重症监护室停留期间的某个时间点，47例（89%）患者发生谵妄。在53例患者中，12例（23%）具有APOE 4等位基因（APOE 4+），41例（77%）仅具有APOE 2或APOE 3等位基因（APOE 4-）。APOE 4+患者更年轻（53.2 +/- 21.9 vs. 65.4 +/- 13.4，p = 0.08），较少因肺炎入院（0% vs. 29.3%，p = 0.05），但他们的谵妄持续时间是APOE 4-患者的两倍：中位数（四分位距），4（3，4.5）vs. 2（1，4）天（p = 0.05）。APOE 4+和APOE 4-患者之间的其他临床结局无显著差异。采用多变量回归分析校正年龄、入院诊断为脓毒症或急性呼吸窘迫综合征或肺炎、疾病严重程度和昏迷持续时间，APOE 4等位基因的存在是谵妄持续时间的最强预测因子（比值比，7.32; 95%可信区间，1.82-29.51，p = 0.005）。APOE 4等位基因代表了人类首次证明的更长时间谵妄的遗传易感性。
Objective., To test for an association between apolipoprotein E (APOE) genotypes and duration of intensive care unit delirium.Design: Prospective, observational cohort study.Setting: A 541-bed, community-based teaching hospital.Patients: Fifty-three mechanically ventilated intensive care unit patients.Interventions. None.Measurements and Main Results., All patents were managed with standardized sedation and ventilator weaning protocols as part of an ongoing clinical trial and were evaluated prospectively for delirium with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). DNA was extracted from whole blood samples obtained on enrollment and APOE genotype was determined using polymerase chain reaction followed by restriction enzyme digestion by investigators blinded to the clinical information. Delirium occurred in 47 (89%) patients at some point during the intensive care unit stay. Of the 53 patients, 12 (23%) had an APOE4 allele (APOE4+) and 41 (77%) had only APOE2 or APOE3 alleles (APOE4-). APOE4+ patients were younger (53.2 +/- 21.9 vs. 65.4 +/- 13.4, p =.08) and less often admitted for pneumonia (0% vs. 29.3%, p =.05) compared with APOE4- patients, yet they had a duration of delirium that was twice as long: median (interquartile range), 4 (3, 4.5) vs. 2 (1, 4) days (p =.05). No other clinical outcomes were significantly different between the APOE4+ and APOE4- patients. Using multivariable regression analysis to adjust for age, admission diagnosis of sepsis or acute respiratory distress syndrome or pneumonia, severity of illness, and duration of coma, the presence of APOE4 allele was the strongest predictor of delirium duration (odds ratio, 7.32; 95% confidence interval, 1.82-29.51, p =.005).Conclusions. APOE4 allele represents the first demonstrated genetic predisposition to longer duration of delirium in humans.