Polimorfismos genéticos predictores de mortalidad asociada a shock séptico en pacientes sometidos a cirugía mayor

Abstract

Sepsis is a pathological process due to a dysregulated response to an infection. Severe cases of sepsis can lead to septic shock, which is associated with high morbidity and mortality. Likewise, there is a high heterogeneity in septic patients that conditions their evolution and prognosis. The study and characterization of the differences at the genetic level, and specifically the existence of single nucleotide polymorphisms (SNPs) can contribute to a better understanding of the immunopathogenesis of this disease, aswell as improve its management. Objectives: To study the presence of different SNPs in genes related to the innate immune response and its association with mortality in patients who underwent major surgery and who developed septic shock after surgery. Methods: A retrospective study was carried out on 175 patients who developed septic shock after major surgery at the Hospital Clínico Universitario de Valladolid, between 2008 and2012. A total of fifteen SNPs in four genes related to the innate immune response were selected: a cytokine (Interferon Lambda 3 – IFNL3, analyzed SNP: rs12980275), a marker of subpopulations of neutrophils (Olfactomedin 4 – OLFM4, analyzed SNPs:rs9536339, rs1891944, rs9563130, rs9536343, rs17552047, rs2298229 and rs12552), a surface glycoprotein (Carcinoembryonic antigen-related cell adhesion molecule 7 –CEACAM7, analyzed SNPs: rs1001578, rs10409040, rs59654817 and rs889365) and the receptor of a proinflammatory cytokine (Type I Interleukin 1 Receptor – IL-1R1, SNPs analyzed: rs2110726, rs3917225 and rs6755229). The relationship between these SNPs and 28-day mortality after septic shock diagnosis was assessed using Kaplan-Meier survival curves and multivariate Cox proportional hazards regression, adjusting for the most significant clinical covariates...