Personalized Medicine Genetic Variation and Loss of Physiologic Complexity Are Associated With Mortality in 644 Trauma Patients
Personalized Medicine Genetic Variation and Loss of Physiologic Complexity Are Associated With Mortality in 644 Trauma Patients
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DOI：
10.1097/sla.0b013e181b8fb1f
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发表时间：
2009-10-01
影响因子：
9
通讯作者：
Morris, John A., Jr.
中科院分区：
文献类型：
--
作者：
Norris, Patrick R.;Canter, Jeffrey A.;Morris, John A., Jr.
目的：个性化医疗融合遗传学。生理复杂性（心率[HR]变异性）的丧失是自主神经系统（ANS）功能障碍的床边生物标志物。我们假设ANS受体蛋白的变异（基因）和复杂性的丧失（生理）与危重疾病的死亡率独立相关。HR复杂性的降低与创伤和其他危重疾病人群中死亡率和发病率的增加有关- 1a和-2肾上腺素能受体（ADRA1A, ADRB2）的遗传变异与各种组织中平滑肌张力的变化有关，并与支气管高反应性有关。代谢综合征和其他疾病。方法：对644例创伤重症监护病房（ICU）入院患者的复杂性数据和遗传样本进行队列分析。两种ANS受体多态性（rs1048101， Alpha ADRA1A和rs1042714， Beta ADRB2）在ICU住院期间的不同时间点的生理复杂性使用先前研究的整数HR多尺度熵（MSE）测量6小时间隔（类似于21,1600 HR数据点/间隔/患者）逻辑回归评估基因型的并发关系。的复杂性。生存概率（包含年龄、损伤机制/ 70和入院生命体征的急性评分）与死亡风险的关系结果：96例患者（15%）死亡。非幸存者早期的复杂性较低。在ICU住院的中期和后期（非幸存者的中位MSE至少降低25%，P < 0.001）和GG ADRB2基因型的发生率较低（7.5% vs. 18.3%, P < 0.001）。在多变量logistic回归中，GG ADRB2基因型的死亡率降低了3倍（奇比[OR] = 0.33）。P = 0.01)，独立于HR MSE （OR= 0.93 P < 0.001）和生存概率（OR=0.22）的显著影响。P < 0.001)结论：这是第一个同时检测ANS遗传、生物标志物复杂性和死亡率的研究。(1) ANS的遗传和生理复杂性与死亡率独立相关。(2)遗传学和复杂性在传统的灵敏度核心（生存概率）上增加了信息；(3)同时评估ANS生理学和遗传学可能产生新的研究和诊断。以及危重疾病的治疗机会
Objective: Personalized medicine merges genetics. physiology, and patient outcome Loss of physiologic complexity (heart rate [HR] variability) is a bedside biornarker for autonomic nervous system (ANS) dysfunction. We hypothesized that variability in ANS receptor proteins (genelics) and loss of complexity ( physiology) are independently associated with mortality in critical illnessSummary Background Data: Decreased HR complexity has been associated with increased mortality and morbidity in trauma and other critically ill populations Genetic variations in alpha-1A and beta-2 adrenergic receptors (ADRA1A, ADRB2) have been associated with changes in smooth muscle tone in various tissues, and implicated in bronchial hyper-responsiveness. metabolic syndrome and other disorders.Methods: A cohort of 644 trauma intensive care unit (ICU) admissions had complexity data and genetic samples. Two ANS receptor polymorphisms (rs1048101, Alpha ADRA1A and rs1042714, Beta ADRB2) were genotyped Physiologic complexity at various points in the ICU stay was measured using previously-studied integer HR multiscale entropy (MSE) over 6-hour intervals (similar to 21,1600 HR data points/interval/patient) Logistic regression assessed the concurrent relationship of genotypes. complexity. and probability of survival, an acuity score incorporating age, injury mechanism/ seventy, and admission vitals, to risk of deathResults: Of total, 96 patients (15%) died. Nonsurvivors had lower complexity at early. middle, and late portions of ICU stay (median MSE at least 25% less in nonsurvivors, P < 0.001) and lower incidence of the GG ADRB2 genotype (7.5% vs. 18.3%, P < 0.001) In muluvariable logistic regression, the GG ADRB2 genotype carried similar to 3-fold decrease in mortality odds (odd ratio [OR] = 0.33. P = 0.01), independent of significant effects in HR MSE (OR = 0.93 P < 0.001), and probability of survival (OR=0.22. P < 0.001)Conclusions: This first study to simultaneously examine ANS genetics, the biomarker complexity, and mortality concludes. (1) ANS genetics and physiologic complexity are independently related to mortality. (2) Genetics and complexity add information over traditional acuity coring (probability of survival), and (3) Simultaneous assessment of ANS physiology and genetics may yield novel research, diagnostic. and therapeutic opportunities in critical illness