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OLFM4 多态性可预测重大手术后脓毒性休克的存活。

OLFM4 polymorphisms predict septic shock survival after major surgery.

机构信息

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.

出版信息

Eur J Clin Invest. 2021 Apr;51(4):e13416. doi: 10.1111/eci.13416. Epub 2020 Oct 14.

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.

摘要

背景

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。

材料和方法

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。

结果

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)。

结论

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。

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