IFNL3 rs12980275 Polymorphism Predicts Septic Shock-Related Death in Patients Undergoing Major Surgery: A Retrospective Study

Felipe Pérez-García,Pedro Martínez-Paz,Amanda Fernández-Rodríguez,María Heredia-Rodríguez,Pablo Jorge-Monjas,Estefanía Gómez-Pesquera,Susana Soria,Salvador Resino,Maria Ángeles Jiménez-Sousa,Eduardo Tamayo,Esther Gómez-Sánchez

doi:10.3389/fmed.2020.00186

Abstract

Interferon lambda 3 (IFNL3, previously called IL-28B) is a cytokine with effects against viral and bacterial pathogens. We aimed to analyze the IFNL3 rs12980275 SNP in patients who underwent major surgery, in order to establish its relationship with susceptibility to septic shock and septic shock-related death in these patients. We performed a case-control study on 376 patients to establish the association between IFNL3 rs12980275 SNP and the susceptibility to develop septic shock. Besides, we performed a longitudinal study among 172 septic shock patients using survival analysis with one censoring point of 28-days mortality. The IFNL3 rs12980275 polymorphism was genotyped by Agena Bioscience's MassARRAY platform. IFNL3 rs12980275 polymorphism was not associated with higher susceptibility to infection and septic shock development. Regarding survival analysis, the Kaplan–Meier analysis showed that patients with IFNL3 rs12980275 AA genotype had higher survival than patients with GG genotype (p = 0.003). The Cox regression analysis adjusted by the most relevant clinical and epidemiological characteristics showed that the GG genotype (recessive model) and the presence of the G allele (additive model) were associated with higher risk of death [adjusted hazard ratio (aHR) = 2.15, p = 0.034; aHR = 1.50, p = 0.030, respectively]. In conclusion, IFNL3 rs12980275 polymorphism was associated with septic shock-related death in patients who underwent major surgery. The A allele was linked to protection, and the G allele was associated with an increased risk of death. This is a first preliminary study that suggests for the first time a role of IFNL3 polymorphisms in the prognosis of septic shock.

Highlights

Sepsis is a life-threatening disease, defined as a syndrome of organ dysfunction due to a dysregulated host response to an infection [1]
The genotypic frequencies of IFNL3 rs12980275 polymorphism were very similar between the SS-group and the SIRS-group (Figure 1A)
The rs12980275 polymorphism was not associated with susceptibility to the development of septic shock, regardless of the inheritance model analyzed

Summary

Introduction

Sepsis is a life-threatening disease, defined as a syndrome of organ dysfunction due to a dysregulated host response to an infection [1]. The incidence of sepsis has grown worldwide and has been reported as the most common cause of Intensive Care Unit (ICU) admission [2]. This disease affects more frequently elderly patients, being especially common in patients with cancer or underlying immunosuppression [3]. Sepsis-related death is decreasing in the last years [4, 5], it remains unacceptably high, accounting as the most frequent cause of death in ICU patients, and constituting a significant cost for healthcare systems [6]. The research of predictors of morbidity and mortality constitutes a priority in order to provide adequate management of patients with sepsis [8]

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