Auswirkungen einer Variation im TREM-1-Gen auf die Mortalität bei septischen Patienten

by Julius Runzheimer
Doctoral thesis
Date of Examination:2024-02-20
Date of issue:2024-02-12
Advisor:Prof. Dr. Ashham Mansur
Referee:PD Dr. Marian Grade
Referee:Prof. Dr. Ralf Dressel
Persistent Address: http://dx.doi.org/10.53846/goediss-10347

 

 

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Abstract

English

Sepsis is a life-threatening organ dysfunction caused by a disturbed immune response of the organism to an infectious agent. Sepsis is one of the most common causes of death in intensive care units. Due to its epidemiology and the high cost of treatment, sepsis represents a significant burden on the healthcare system. The variable clinical presentation, complex therapy and different patient responses to interventions make sepsis a formidable challenge for healthcare professionals. The Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) plays a central role in inflammatory reactions as part of the innate immune response and enhances the immune response when activated. In sepsis, excessive activation and/or inadequate inhibition of the immune system leads to organ dysfunction. Single nucleotide polymorphisms (SNPs) play a critical role in the pathophysiology, clinical manifestation, treatment response, disease progression, and mortality of sepsis. Identification of SNPs with significant impact on sepsis could aid in the development of prognostic tools, diagnostic tests, and targeted therapies. Such advances would be particularly beneficial given the current lack of standardized tests or laboratory parameters to diagnose and treat causative sepsis. There is currently research examining the impact of TREM-1 variations on the progression of sepsis. In this study, we investigated the possible effect of the SNP rs2234237 in the TREM-1 gene on disease progression, severity and mortality in septic Caucasian patients. The study involved 649 prospectively included patients who developed sepsis during their intensive care stay at the University Medical Center Göttingen (UMG). During the course of intensive therapy, data on the severity of the disease and mortality of the patients were carefully documented. The TREM-1 genotype rs2234237 was determined using blood samples and real-time polymerase chain reaction. In our study, TREM-1 genotype rs2234237 had no significant impact on sepsis mortality or progression. In addition, the genotype could not serve as a reliable predictor of a potentially severe course of the disease. This finding contributes to a deeper understanding of the pathophysiology of sepsis and the importance of genetic variations in the TREM-1 gene in this context. Further studies on other TREM-1 SNPs and additional components of the TREM-1 signaling pathway are required to fully elucidate the role of this protein in sepsis.
Keywords: sepsis; 90-day mortality; TREM-1; single nucleotide polymorphism; survival analysis
 
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