Impact of glucocorticoid receptor polymorphism rs6198 on sepsis survival in a prospective multicenter cohort

作者：Christoph Sombetzki, Lars Palmowski, Dominik Ziehe, Hartmuth Nowak, Tim Rahmel, Stefan Ehrentraut, Patrick Thon, Jennifer Orlowski, Lars Bergmann, Michael Adamzik, Björn Koos, Katharina Rump, Michael Adamzik, Moritz Anft, Thorsten Annecke, Nina Babel, Maha Bazzi, Lars Bergmann, Christian Bode, Thilo Bracht, Alexander von Busch, Jérôme Defosse, Stefan Ehrentraut, Martin Eisennacher, Björn Ellger, Christian Ertmer, Ulrich H. Frey, Katrin Fuchs, Helge Haberl, Dietrich Henzler, Daniel Kleefisch, Thomas Köhler, Björn Koos, Ulrich Limper, Katrin Marcus, Hartmuth Nowak, Daniel D. Oswald, Christian Putensen, Tim Rahmel, Katharina Rump, Jens‐Christian Schewe, Elke Schwier, Barbara Sitek, Matthias Unterberg, Frank Wappler, Katrin Willemsen, Alexander Wolf, Alexander Zarbock, Birgit Zuelch · 发表于：Scientific Reports · 年份：2025 · DOI：10.1038/s41598-025-07398-4 · 被引用次数：3 · 研究领域：Sepsis Diagnosis and Treatment、Neutropenia and Cancer Infections、Adrenal Hormones and Disorders

The glucocorticoid receptor (GR), particularly its isoforms GRα and GRβ, plays a crucial role in modulating inflammatory responses. The rs6198 single nucleotide polymorphism (SNP) in the NR3C1 gene, which encodes GR, has been associated with adverse outcomes in various diseases due to its potential effect on GR isoform expression. This study aims to explore the impact of the rs6198 SNP in sepsis. Specifically, we tested the hypothesis that the presence of a particular genotype of the rs6198 SNP is associated with an increased 30-day mortality rate in patients with sepsis. This prospective, multicenter study included 204 ICU patients diagnosed with sepsis, as part of the Sepsis.Data.Net NRW cohort. Genotyping for rs6198 and immunofluorescence as well as quantification of GR expression were performed. Statistical analyses included Hardy-Weinberg equilibrium, Kaplan-Meier survival analysis, log-rank tests, multivariate Cox regression, and logistic regression. Genotyping for the rs6198 SNP identified 137 patients (67%) with the TT- and 67 (33%) with CC/CT-genotype. Patients with the TT-genotype had a 30-day survival rate of 65% (89 of 137 patients), which was significantly lower than the 82% survival rate (55 of 67 patients) observed in the patients with the CC/CT-genotype (p = 0.006). A multivariate Cox regression analysis, adjusted for age, SOFA and SAPS2 score, and selected laboratory values, revealed that the TT-genotype was independently associated with an increased risk of ...