Toll-like receptor 1 polymorphisms and associated outcomes in sepsis after traumatic injury: a candidate gene association study.
Toll-like receptor 1 polymorphisms and associated outcomes in sepsis after traumatic injury: a candidate gene association study.
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DOI：
10.1097/sla.0b013e31828538e8
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发表时间：
2014-01
影响因子：
9
通讯作者：
Wurfel MM
中科院分区：
文献类型：
--
作者：
Thompson CM;Holden TD;Rona G;Laxmanan B;Black RA;OʼKeefe GE;Wurfel MM
确定TLR1中的SNPs是否与创伤人群中的死亡率，特别是败血症相关死亡率有关。由Toll样受体(Toll-like Receptor，TLRs)介导的先天免疫反应，诱导对病原体和损伤相关分子模式的早期炎症反应。在一些传染性和非传染性疾病状态下，TLRs的遗传变异与易感性和预后有关。在服务于4个州的一级创伤中心的创伤重症监护病房的患者被纳入，并跟踪观察感染、败血症和死亡的发展。对基因组DNA进行基因分型，并进行Logistic回归分析，以确定TLR1SNP与死亡率之间的关联。我们根据脓毒症的存在和败血症相关生物体的类型，进一步研究了TLR1单核苷酸多态与死亡率之间的相关性。我们招募了1,961名患者。TLR1-7202G(Rs5743551)与创伤后死亡率的增加相关，这种关联主要观察到发生脓毒症的患者(调整后的OR3.16；95%可信区间1.43-6.97，P=0.004)。在进一步限制革兰氏阳性脓毒症后，这种关联仍然存在。TLR1742A/G(Asn248Ser)(Rs4833095)也与革兰氏阳性脓毒症患者的死亡率相关(校正OR4.16；95%CI1.22~14.19，P=0.023)。TLR1的基因变异与创伤后脓毒症患者死亡率的增加有关，并可能代表危重创伤患者死亡风险的新标志。
To determine if SNPs in TLR1 are associated with mortality, specifically sepsis-associated mortality, in a traumatically injured population. Innate immune responses mediated by toll-like receptors (TLRs), induce early inflammatory responses to pathogen and damage-associated molecular patterns. Genetic variation in TLRs has been associated with susceptibility and outcomes in a number of infectious and non-infectious disease states. Patients admitted to the trauma intensive care unit at a level one trauma center serving 4 states were enrolled and followed for development of infection, sepsis, and death. Genomic DNA was genotyped and logistic regression analysis performed to determine associations between TLR1 SNPs and mortality. We further examined for associations between TLR1 SNPs and mortality in subgroups based on the presence of sepsis and the type of sepsis-associated organism. We enrolled 1,961 patients.TLR1-7202G (rs5743551) was associated with increased mortality after traumatic injury and this association was primarily observed in the subset of patients who developed sepsis (adjusted OR 3.16; 95% CI 1.43–6.97, P=0.004). This association persisted after further restriction to gram-positive sepsis. TLR1742A/G(Asn248Ser) (rs4833095), a coding SNP in LD with TLR1-7202Gwas also associated with mortality in gram-positive sepsis (adjusted OR 4.16; 95% CI 1.22–14.19, P=0.023). Genetic variation in TLR1 is associated with increased mortality in patients with sepsis following traumatic injury and may represent a novel marker of risk for death in critically injured patients.