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基因多态性与危重症患者脓毒症不良结局的关联。

Association of Gene Polymorphism with Adverse Outcomes of Sepsis in Critically Ill Patients.

机构信息

Medical Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia.

Critical Care Department, ALNoor Specialist Hospital, Makkah, Kingdom of Saudi Arabia.

出版信息

DNA Cell Biol. 2020 Sep;39(9):1723-1729. doi: 10.1089/dna.2020.5468. Epub 2020 Jul 17.

DOI:10.1089/dna.2020.5468
PMID:32700971
Abstract

Sepsis-related mortality and morbidity are major health care problems worldwide. More effort is required to identify factors associated with adverse outcome. Evaluate the prognostic capacity of tumor necrosis factor (TNF), kidney injury molecule (KIM), and lactate and gene polymorphism for prediction of 28 days-intensive care unit (ICU) mortality. single nucleotide polymorphisms was detected by real-time-PCR on 112 had septic shock and 88 were septic. Serum TNF-α and urinary KIM were assessed by enzyme-linked immunosorbent assay. This study included 200 critically ill patients, 125 (62.5%) of them died within 28 days in ICU (nonsurvivors). Frequencies of was (70.7) GG, (28) GA and (1.3) AA in survivors versus (85.6) GG, (12) GA and (2.4) AA for nonsurvivors, revealed significant association with ICU mortality but not sepsis severity ( = 0.15) or sepsis-induced acute kidney injury (AKI). In contrast, urinary KIM-1 revealed significant association with sepsis severity ( = 0.036) and AKI ( = 0.0001), but not 28-days ICU mortality. The relative risk of death in patients with GG genotype was 2.5 mainly in ICU younger male patients (odds ratios 24 and 4.9,  = 0.001). The genotype GG and GA were significantly associated with [increased urinary KIM-1 (0.29 ± 0.1) ( = 0.0001), terminal creatinine (1.67 ± 0.8) ( = 0.0001)] and [increased terminal urea (109 ± 0.001) ( = 0.001) and basal serum TNF (60 ± 0.001) ( = 0.0001)], respectively. In linear regression analysis, AKI 0.0001 (0.4-0.67), basal serum TNF 0.04 (0.0001-0.04), and 0.007 (0.05-0.33) were associated with 28 days ICU mortality [ value (95% confidence interval)]. The same results were observed for initial urea 0.024 (0.0001-0.003) and lack of diuretic usage 0.0001 (0.35-0.7) mainly in septic patients. Major frequency of polymorphism (mainly in young age male patients), AKI and serum TNF were associated with increased risk for 28 days-ICU mortality. Furthermore, sepsis severity was influenced by TNF and urinary KIM-1, which reflects in AKI.

摘要

脓毒症相关的死亡率和发病率是全球主要的医疗保健问题。需要更多的努力来确定与不良预后相关的因素。评估肿瘤坏死因子 (TNF)、肾损伤分子 (KIM) 和乳酸以及基因多态性对预测 28 天重症监护病房 (ICU)死亡率的预后能力。通过实时聚合酶链反应检测 112 例脓毒性休克和 88 例脓毒症患者的单核苷酸多态性。通过酶联免疫吸附试验评估血清 TNF-α 和尿 KIM。这项研究包括 200 名危重病患者,其中 125 名 (62.5%)在 ICU 28 天内死亡 (非幸存者)。幸存者的 频率为 (70.7) GG、(28) GA 和 (1.3) AA,而非幸存者为 (85.6) GG、(12) GA 和 (2.4) AA,与 ICU 死亡率显著相关,但与脓毒症严重程度 ( = 0.15)或脓毒症引起的急性肾损伤 (AKI)无关。相比之下,尿 KIM-1 与脓毒症严重程度 ( = 0.036)和 AKI ( = 0.0001)显著相关,但与 28 天 ICU 死亡率无关。GG 基因型患者死亡的相对风险为 2.5,主要发生在 ICU 年轻男性患者 (比值比 24 和 4.9, = 0.001)。基因型 GG 和 GA 与 [尿 KIM-1 升高 (0.29±0.1) ( = 0.0001),终末期肌酐 (1.67±0.8) ( = 0.0001)] 和 [终末期尿素升高 (109±0.001) ( = 0.001)和基础血清 TNF (60±0.001) ( = 0.0001)]显著相关。在线性回归分析中,AKI 0.0001 (0.4-0.67)、基础血清 TNF 0.04 (0.0001-0.04)和 0.007 (0.05-0.33)与 28 天 ICU 死亡率相关 [ 值 (95%置信区间)]。初始尿素 0.024 (0.0001-0.003)和缺乏利尿剂使用 0.0001 (0.35-0.7)也观察到相同的结果,主要发生在脓毒症患者中。主要的 多态性 (主要发生在年轻男性患者)、AKI 和血清 TNF 与 28 天 ICU 死亡率增加的风险相关。此外,TNF 和尿 KIM-1 影响脓毒症的严重程度,这反映在 AKI 中。

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