OLFM4 polymorphisms predict septic shock survival after major surgery.

Pérez-García, Felipe; Resino, Salvador; Gómez-Sánchez, Esther; Gonzalo-Benito, Hugo; Fernández-Rodríguez, Amanda; Lorenzo-López, Mario; Heredia-Rodríguez, María; Gómez-Pesquera, Estefanía; Tamayo, Eduardo; Jiménez-Sousa, Maria Ángeles

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=0.024) and patients with rs1891944 CC/CT genotype (p-value=0.038). 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=0.065). 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.