The FER rs4957796 TT genotype is associated with unfavorable 90-day survival in Caucasian patients with severe ARDS due to pneumonia

José Hinz,Fabian Kriesel,Ingo Bergmann,Michael Ghadimi,Mladen Tzvetkov,Benedikt Büttner,Ashham Mansur,Aron Frederik Popov,Tim Beissbarth,Maximilian Steinau

doi:10.1038/s41598-017-08540-7

José Hinz, Fabian Kriesel + Show 8 more

Open Access

https://doi.org/10.1038/s41598-017-08540-7

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Abstract

A recent genome-wide association study showed that a genetic variant within the FER gene is associated with survival in patients with sepsis due to pneumonia. Because severe pneumonia is the main cause of acute respiratory distress syndrome (ARDS), we aimed to investigate the effect of the FER polymorphism rs4957796 on the 90-day survival in patients with ARDS due to pneumonia. An assessment of a prospectively collected cohort of 441 patients with ARDS admitted to three intensive care units at the University Medical Centre identified 274 patients with ARDS due to pneumonia. The 90-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores and organ support-free days were used as the secondary variables. FER rs4957796 TT-homozygous patients were compared with C-allele carriers. The survival analysis revealed a higher 90-day mortality risk among T homozygotes than among C-allele carriers (p = 0.0144) exclusively in patients with severe ARDS due to pneumonia. The FER rs4957796 TT genotype remained a significant covariate for the 90-day mortality risk in the multivariate analysis (hazard ratio, 4.62; 95% CI, 1.58–13.50; p = 0.0050). In conclusion, FER rs4957796 might act as a prognostic variable for survival in patients with severe ARDS due to pneumonia.

Highlights

Acute respiratory distress syndrome (ARDS) is characterized by excessive and protracted pulmonary inflammation with increased permeability of pulmonary capillary and alveolar epithelial cells, leading to hypoxemia that is refractory to the usual oxygen therapy[1, 2]
Because the most frequent lung condition leading to acute respiratory distress syndrome (ARDS) is sepsis due to pneumonia[19, 20], this study aimed to investigate the effect of the FER rs4957796 variant on the 90-day survival in patients with ARDS due to pneumonia according to the severity of ARDS
A total of 274 adult Caucasian patients with ARDS due to pneumonia were enrolled in this study

Summary

Introduction

Acute respiratory distress syndrome (ARDS) is characterized by excessive and protracted pulmonary inflammation with increased permeability of pulmonary capillary and alveolar epithelial cells, leading to hypoxemia that is refractory to the usual oxygen therapy[1, 2]. Attempts to reduce the mortality in ARDS patients by decreasing the overwhelming pulmonary inflammation have proven mostly disappointing[6,7,8], most likely because these interventions have usually been applied unselectively to heterogeneous groups of patients, without considering the potential influence of host genetic diversity on the response to treatment. A recent genome-wide association study has shown that a genetic variant within the intronic region of the FER gene, rs4957796, is associated with survival in patients with sepsis due to pneumonia. FER impacts leucocyte recruitment and intestinal barrier dysfunction in response to bacterial lipopolysaccharides[15, 16], findings relevant to the potential mechanisms through which variants in this gene could influence sepsis survival. Neutrophil recruitment to the site of infection is essential in innate immune defense, and changes in relevant signaling pathways could lead to a failure to clear bacterial infections or the promotion of further tissue damage[18]

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