Department of Surgery, University of Texas Southwestern Medical Center at Dallas, Texas, USA.
Shock. 2010 Jan;33(1):19-23. doi: 10.1097/SHK.0b013e3181a99508.
Impaired mitochondrial activity has been linked to increased risk for clinical complications after injury. Furthermore, variant mitochondrial alleles have been identified and are thought to result in decreased mitochondrial activity. These include a nonsynonymous mitochondrial polymorphism (T4216C) in the nicotinamide adenine dinucleotide dehydrogenase 1 gene (ND1), encoding a key member of complex I within the electron transport chain, which is found almost exclusively among Caucasians. We hypothesized that burn patients carrying ND1 4216C are less able to generate the cellular energy necessary for an effective immune response and are at increased risk for infectious complications. The association between 4216C and outcome after burn injury was evaluated in a cohort of 175 Caucasian patients admitted to the Parkland Hospital with burns covering greater than or equal to 15% of their total body surface area or greater than or equal to 5% full-thickness burns under an institutional review board-approved protocol. To remove confounding unrelated to burn injury, individuals were excluded if they presented with significant non-burn-related trauma (Injury Severity Score > or =16), traumatic or anoxic brain injury, spinal cord injury, were HIV/AIDS positive, had active malignancy, or survived less than 48 h postadmission. Within this cohort of patients, carriage of the 4216C allele was significantly associated by unadjusted analysis with increased risk for sepsis-related organ dysfunction or septic shock (P = 0.011). After adjustment for full-thickness burn size, inhalation injury, age, and sex, carriage of the 4216C allele was associated with complicated sepsis (adjusted odds ratio = 3.7; 95% confidence interval, 1.5-9.1; P = 0.005), relative to carriers of the T allele.
线粒体活性受损与损伤后临床并发症风险增加有关。此外，已经确定了变异的线粒体等位基因，并且认为这些等位基因导致线粒体活性降低。其中包括烟酰胺腺嘌呤二核苷酸脱氢酶 1 基因（ND1）中的一个非同义线粒体多态性（T4216C），该基因编码电子传递链中复合体 I 的关键成员，几乎仅在白种人中发现。我们假设携带 ND1 4216C 的烧伤患者生成有效免疫反应所需的细胞能量的能力较低，并且感染并发症的风险增加。在一项机构审查委员会批准的方案中，对入住 Parkland 医院的 175 名白人烧伤患者进行了队列研究，这些患者的烧伤面积大于或等于 15%的体表面积，或大于或等于 5%的全层烧伤。为了消除与烧伤无关的混杂因素，如果患者存在严重的非烧伤相关创伤（损伤严重程度评分≥16）、创伤性或缺氧性脑损伤、脊髓损伤、HIV/AIDS 阳性、活动性恶性肿瘤或入院后 48 小时内存活，则将其排除在外。在这组患者中，未经调整的分析显示，携带 4216C 等位基因与脓毒症相关器官功能障碍或感染性休克的风险增加显著相关（P=0.011）。在校正全层烧伤面积、吸入性损伤、年龄和性别后，携带 4216C 等位基因与复杂的脓毒症相关（校正优势比=3.7；95%置信区间，1.5-9.1；P=0.005），与 T 等位基因携带者相比。
