Barber R C, Aragaki C C, Rivera-Chavez F A, Purdue G F, Hunt J L, Horton J W
The Department of Surgery, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9160, USA.
J Med Genet. 2004 Nov;41(11):808-13. doi: 10.1136/jmg.2004.021600.
Sepsis, organ failure, and shock remain common among patients with moderate to severe burn injuries. The inability of clinical factors to identify at-risk patients suggests that genetic variation may influence the risk for serious infection and the outcome from severe injury.
Resolution of genetic variants associated with severe sepsis following burn injury.
A total of 159 patients with burns > or =20% of their total body surface area or any smoke inhalation injury without significant non-burn related trauma (injury severity score (ISS)> or =16), traumatic or anoxic brain injury, or spinal cord injury and who survived more than 48 h post-admission.
Candidate single nucleotide polymorphisms (SNPs) within bacterial recognition (TLR4 +896, CD14 -159) and inflammatory response (TNF-alpha -308, IL-1beta -31, IL-6 -174) loci were evaluated for association with increased risk for severe sepsis (sepsis plus organ dysfunction or septic shock) and mortality.
After adjustment for age, full-thickness burn size, ethnicity, and gender, carriage of the TLR4 +896 G-allele imparted at least a 1.8-fold increased risk of developing severe sepsis following a burn injury, relative to AA homozygotes (adjusted odds ratio (aOR) 6.4; 95% confidence interval (CI) 1.8 to 23.2). Carriage of the TNF-alpha -308 A-allele imparted a similarly increased risk, relative to GG homozygotes (aOR = 4.5; 95% CI 1.7 to 12.0). None of the SNPs examined were significantly associated with mortality.
The TLR4 +896 and TNF-alpha -308 polymorphisms were significantly associated with an increased risk for severe sepsis following burn trauma.
脓毒症、器官衰竭和休克在中重度烧伤患者中仍然很常见。临床因素无法识别高危患者，这表明基因变异可能影响严重感染风险和严重损伤的预后。
确定烧伤后与严重脓毒症相关的基因变异。
共159例烧伤面积≥20%体表面积或有任何烟雾吸入性损伤、无严重非烧伤相关创伤（损伤严重度评分（ISS）≥16）、无创伤性或缺氧性脑损伤或脊髓损伤且入院后存活超过48小时的患者。
评估细菌识别（TLR4 +896、CD14 -159）和炎症反应（TNF-α -308、IL-1β -31、IL-6 -174）位点内的候选单核苷酸多态性（SNP）与严重脓毒症（脓毒症加器官功能障碍或感染性休克）风险增加及死亡率的相关性。
在调整年龄、全层烧伤面积、种族和性别后，与AA纯合子相比，携带TLR4 +896 G等位基因使烧伤后发生严重脓毒症的风险至少增加1.8倍（调整优势比（aOR）6.4；95%置信区间（CI）1.8至23.2）。与GG纯合子相比，携带TNF-α -308 A等位基因也使风险有类似增加（aOR = 4.5；95% CI 1.7至12.0）。所检测的SNP均与死亡率无显著相关性。
TLR4 +896和TNF-α -308多态性与烧伤创伤后严重脓毒症风险增加显著相关。
