Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain.
Departamento de Anestesiología y Reanimación, Hospital Clínico Universitario, Valladolid, Spain.
Eur J Clin Invest. 2021 Apr;51(4):e13416. doi: 10.1111/eci.13416. Epub 2020 Oct 14.
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.
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.
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).
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.
嗅球蛋白 4(OLFM4)是一种受核因子-κB(NF-κB)调控的基因,其高表达与脓毒症休克患者器官衰竭和死亡的风险增加有关。我们旨在评估 175 名接受大手术的患者中 OLFM4 单核苷酸多态性(SNP)与脓毒症休克相关死亡的相关性,以及其在预测死亡率方面的性能。
我们进行了一项回顾性研究。通过 Agena Bioscience 的 MassARRAY 平台对总共 7 个 OLFM4 SNP 进行基因分型。通过 Kaplan-Meier 和 Cox 回归检验进行统计分析。通过接受者操作特征(ROC)曲线下面积(AUROC)评估预测脓毒症休克相关死亡的诊断性能。
与 rs17552047 G 等位基因(P 值=0.024)和 rs1891944 CC/CT 基因型(P 值=0.038)相比,rs17552047 A 等位基因和 rs1891944 TT 基因型的患者具有更高的生存率。然而,只有 rs17552047 与加性遗传模型下较低的死亡风险相关(调整后的危险比[aHR]=0.44,95%CI=0.27-0.71)。包含最显著临床变量(乳酸、慢性肾脏病、腹膜炎、心脏病和择期手术)的多变量模型显示,预测脓毒症休克相关死亡的 AUROC 为 0.776。当我们将 OLFM4 rs17552047 SNP 添加到之前的模型中时,AUROC 为 0.811,且接近与之前的模型有显著差异(P 值=0.065)。
OLFM4 rs17552047 A 等位基因预测接受大手术的患者脓毒症的生存情况。此外,rs17552047 与临床变量一起可用于预测脓毒症的结局。