OLFM4 polymorphisms predict septic shock survival after major surgery

Abstract

Background Higher expression of olfactomedin‐4 (OLFM4), a gene regulated by nuclear factor‐kappa B (NF‐κB), has been related to a higher risk of organ failure and death in patients with septic shock. We aimed to evaluate the association between OLFM4 single nucleotide polymorphisms (SNPs) and septic shock‐related death in 175 patients who underwent major surgery, as well as its performance in predicting mortality. Materials and methods We carried out a retrospective study. A total of seven OLFM4 SNPs were genotyped by Agena Bioscience's MassARRAY platform. Statistical analysis was performed by Kaplan‐Meier and Cox regression tests. The diagnostic performance for predicting septic shock‐related death was evaluated by the area under the receiver‐operating characteristic (AUROC) curve. Results Patients with rs17552047 A allele and rs1891944 TT genotype had higher survival than patients with rs17552047 G allele (P‐value = .024) and patients with rs1891944 CC/CT genotype (P‐value = .038). However, only rs17552047 was associated with a lower risk of death under an additive inheritance model (adjusted hazard ratio [aHR] = 0.44, 95% CI = 0.27‐0.71). The multivariate model with the most significant clinical variables (lactate, chronic kidney disease, peritonitis, heart disease and elective surgery) showed an AUROC of 0.776 for predicting septic shock‐related death. When we added the OLFM4 rs17552047 SNP to the previous model, the AUROC was 0.811 and was close to reaching significant differences with the previous model (P‐value = .065). Conclusion OLFM4 rs17552047 A allele predicts septic shock survival in patients who underwent major surgery. Furthermore, rs17552047, together with clinical variables, could be useful to predict the outcome of septic shock.

Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets

“…Other genes, such as olfactomedin-4, are associated with an increased risk of organ failure and death. However, patients with the rs17552047 A allele and the rs1891944 TT genotype have been shown to have higher survival rates than patients with the rs1891944 CC/CT genotype and rs17552047 G allele [ 68 ]. Additionally, the Arg-304-His substitution, which is induced by the rs2230349 G-to-A mutation in G protein-coupled receptor kinase 5, has been shown to disrupt the function of G protein-coupled receptor kinase 5 and reduce the IκB-α/nuclear factor (NF)-κB-mediated inflammatory response, ultimately providing genetic protection against sepsis progression and susceptibility to mortality [ 69 ].…”

Establishment and validation of a logistic regression model for prediction of septic shock severity in children

“…A total of six genes, including CREBBP , WDR82 , NCOA1 , ASH1L , TPR , and SF1 , were identified as prognosis-related genes in patients with septic shock via comprehensively analyzing the gene expression spectrum [ 18 ]. OLFM4 polymorphisms were found to be able to anticipate the clinical outcome of septic shock patients after major surgery [ 19 ]. In our study, a logistic regression model was established using data from four vital genes: G0S2 , CTSD , PRUNE2 , and SLC22A4 , to predict the severity of septic shock in children, using the analysis of differentially expressed genes (DEGs) among the survivors, non-survivors and controls.…”