Polymorphisms In HMGB1Associated With Sepsis And Multiple Organ Dysfunction After Severe Blunt Chest Trauma

Part1The change of plasma levels of HMGB1and itssignificance in patients with severe blunt chest traumaObjective: To observe the dynamic changes of plasma high-mobility groupbox1(HMGB1) and tumor necrosis factor-α (TNF-а) in patients withsevere blunt chest trauma, to assess the severity of injury and to predict itsprognostic value.Methods: A total of57consecutive blunt chest trauma patients with anabbreviated injury scale (AIS)chest≥3were included from March2011toDecember2011, and blood samples were taken from the patients everyother day from d1to d7after admission. Plasma concentration of HMGB1and TNF-α were measured by a quantitative ELISA. Development ofpost-traumatic complications was observed and their relations with plasmalevels of HMGB-1and TNF-α were analyzed.Results: Patients’ median age was (44.5±12.6) years and the median injuryseverity score (ISS) was18.4±6.02. Both the plasma levels of HMGB1and TNF-а had positive correlation with ISS (d1: r=0.29, P=0.068vs. r=0.507,P=0.016; d3: r=0.578, P<0.001vs. r=0.411, P=0.021; d5: r=0.645,P<0.001vs. r=0.365, P=0.07; d7: r=0.683, P<0.001vs. r=0.321, P=0.019).There were significantly increase in mean plasma HMGB1levels on d3,5,7in patients with an ISS20or more compared with those with ISS20or less(all P <0.05). Plasma levels of HMGB1showed a higher sensitivity but lessspecificity than TNF-а in prediction of complications occurrence (P<0.05).Conclusions: Plasma levels of HMGB1seem to be most suitable forseverity assessment and prediction of post-traumatic complicationsoccurrence in patients with severe blunt chest trauma.Part2Clinical relevance of single nucleotide polymorphismsof HMGB1gene in patients with severe blunt chest traumaObjective: High-mobility group box1(HMGB1), a late mediator of thesystemic inflammation, is a potentially useful biomarker for predictingoutcome in patients with severe trauma. Genetic variation within patternrecognition receptors for bacterial endotoxin and exotoxin has been shownto be associated with the risk of sepsis and organ dysfunction in criticalillness. Whether the HMGB1genetic variation is associated with sepsissusceptibility is unknown. The aim of this study was to identify tag singlenucleotide polymorphisms of High-mobility group box protein1and their association with the risk of development of complications in patients withsevere blunt chest trauma.Methods: Genetic variation data for the entire HMGB1gene were obtainedfrom the HapMap Project. The genotypes of HMGB1gene polymorphismswere determined using a pyrosequencing method. Whole peripheral bloodsamples obtained immediately after admission. Sepsis morbidity rate andmultiple organ dysfunction scores were accessed.Results: A total of3tag SNPs of the HMGB1gene were selected usingHapMap database and linkage disequilibrium analysis. Among the three tagSNPs of HMGB1, only the rs2249825polymorphism was shown to be wellassociated with higher risk of sepsis in blunt chest trauma patients whilethe other two tag SNPs (rs1412125, rs1045411) did not affect the outcomeof these patients. Furthermore, the rs2249825SNP was associated withMOD scores.Conclusion: A total of3SNPs might act as tag SNPs for the entireHMGB1gene. The rs2249825might be used to provide relevant riskestimate for the development of sepsis and MODS in patients with severeblunt chest trauma.