The Relationship Between IRAK-1 Polymorphism And Sex-Based Different Outcomes Post-Injury

Objective: Clinical researches characterizing the mechanisms responsible for sex-based outcome differences post-injury remain conflicting.IL-1 receptor–associated kinase-1(IRAK-1)plays a central role through the toll-like receptor(TLR)pathway in the activation of nuclear factor-kappa B(NF-?B).We aimed to further characterize the association between the IRAK-1 polymorphism and clinical outcomes in Chinese trauma patients.Methods: A prospective observational cohort study was performed over a 24-month period from 2012 to 2014 in the emergency trauma center of the Shanghai Sixth People's Hospital.Severely injured blunt trauma patients requiring intensive care unit admission were enrolled,whereas patients with isolated brain and complete cervical spinal cord injury were excluded.After admission,detailed data including demographics,injury characteristics and outcomes were recorded.Blood samples were obtained and genotyped for IRAK-1 polymorphism(1595C/T).Outcomes of interest included nosocomial infection(NI),multiple organ failure(MOF)and in-hospital mortality.Logistic regression was used to identify the risk factors for worse outcomes associated with sex and IRAK-1 polymorphism.Results: A total of 588 Chinese trauma patients were enrolled in this cohort.96(16.1%)patients were homozygous for the IRAK-1 TT/T haplotype.Males and females had significant differences in the IRAK-1 genotypes.Compared to male patients,female had a significantly lower incidence of NI(OR=0.489,p=0.035,95%CI: 0.252-0.951),MOF(OR=0.448,p=0.044,95%CI: 0.205-0.978)and mortality(OR=0.281,p=0.032,95%CI: 0.088-0.899).Furthermore,IRAK-1 TT/T haplotype was associated with a less risk of developing NI(OR=0.331,p=0.026,95%CI: 0.125-0.877)and MOF(OR=0.268,p=0.034,95%CI: 0.079-0.902)in trauma patients.Conclusions: the significant sex-based outcome differences were observed after injury.Patients with the TT/T haplotype of the IRAK-1 polymorphism have a significantly lower risk of developing NI and MOF after severe trauma.These data suggest the IRAK-1 polymorphism is functionally significant and may be an important driver of sex based outcome differences post-injury.