OLFM4 polymorphisms predict septic shock survival after major surgery

• Published in: European journal of clinical investigation Vol. 51; no. 4; pp. e13416 - n/a
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-04-2021
• Subjects: Alleles; Cardiovascular diseases; Coronary artery disease; Death; Heart diseases; Heredity; Kidney diseases; Lactic acid; major surgery; Mortality; Nucleotides; Olfactomedin; OLFM4; Patients; Performance prediction; Peritonitis; Regression analysis; rs17552047; Sepsis; Septic shock; Single-nucleotide polymorphism; SNPs; Statistical analysis; Surgery; Survival; SNPs; major surgery; septic shock; OLFM4; rs17552047; survival
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/eci.13416

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.