Gomez Ruben, O'Keeffe Terence, Chang Ling-Yu, Huebinger Ryan M, Minei Joseph P, Barber Robert C
Department of Surgery, University of Texas Southwestern Medical Center at Dallas, Texas 75390-9160, USA.
J Trauma. 2009 Mar;66(3):850-7; discussion 857-8. doi: 10.1097/TA.0b013e3181991ac8.
Numerous studies have linked impaired mitochondrial activity with increased risk for clinical complications after injury. Furthermore, a number of nonsynonymous polymorphisms have been identified within the mitochondrial genome that are believed to impair cellular respiration. These DNA variants include a nonsynonymous polymorphism (T4216C) in the NADH dehydrogenase 1 gene (ND1), which encodes a key member of Complex I of the electron transport chain. We hypothesized that trauma patients who carry the ND1 4216C allele may be less able to generate the cellular energy necessary to mount an effective immune response and are at increased risk for death as well as sepsis complicated by organ dysfunction or shock.
We enrolled a cohort of 136 patients admitted to the Parkland Hospital Surgical intensive care unit (ICU) with significant trauma (Injury Severity Score > or = 16), > or =16 years of age, and with a minimum intensive care unit stay of > or =24 hours under a protocol approved by the UTSW and Parkland IRBs. Patients with brain death, spinal cord injury, active malignancy, HIV/AIDS or who survived <48 hours after admission were excluded. Clinical data were collected prospectively and T4216C was genotyped by polymerase chain reaction-restriction fragment length polymorphism.
After multivariate adjustment for mechanism, severity of injury, units of packed red blood cells given in the first 24 hours, age, gender, and race/ethnicity, carriage of the 4216 C-allele was significantly associated with increased risk for sepsis complicated by organ dysfunction or septic shock (adjusted odds ratio [aOR] = 3.68; 95%CI: 1.17-11.52; p = 0.02) as well as death (aOR = 4.56; 95% CI: 1.05-19.79; p = 0.04), relative to carriers of the T-allele.
Carriage of the mitochondrial 4216C-allele increases the risk for infectious complications and death after severe trauma.
众多研究已将线粒体活性受损与损伤后临床并发症风险增加联系起来。此外，在线粒体基因组内已鉴定出一些非同义多态性，据信这些多态性会损害细胞呼吸。这些DNA变异包括烟酰胺腺嘌呤二核苷酸脱氢酶1基因（ND1）中的一个非同义多态性（T4216C），该基因编码电子传递链复合体I的一个关键成员。我们推测，携带ND1 4216C等位基因的创伤患者可能较难产生有效免疫反应所需的细胞能量，并且死亡风险以及并发器官功能障碍或休克的脓毒症风险会增加。
我们纳入了136例入住帕克兰医院外科重症监护病房（ICU）的患者，这些患者有严重创伤（损伤严重度评分≥16）、年龄≥16岁，且在得克萨斯大学西南医学中心和帕克兰医院机构审查委员会批准的方案下，在ICU至少停留24小时。排除脑死亡、脊髓损伤、活动性恶性肿瘤、HIV/AIDS患者或入院后存活时间不足48小时的患者。前瞻性收集临床数据，并通过聚合酶链反应-限制性片段长度多态性对T4216C进行基因分型。
在对损伤机制、损伤严重程度、入院后最初24小时输注的红细胞单位数、年龄、性别和种族/民族进行多变量调整后，与T等位基因携带者相比，携带4216 C等位基因与并发器官功能障碍或感染性休克的脓毒症风险增加（调整优势比[aOR]=3.68；95%置信区间：1.17-11.52；p=0.02）以及死亡风险增加（aOR=4.56；95%置信区间：1.05-19.79；p=0.04）显著相关。
线粒体4216C等位基因的携带增加了严重创伤后感染并发症和死亡的风险。
