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Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate thepredisposition to septic shock

机译:白介素10 rs2227307和CXCR2 rs1126579多态性可调节感染性休克的易感性

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摘要

Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α, interlelukin (IL)-1β, IL-10, IL-8, Toll-like receptor 4, CXCR1 and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10 rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2 rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment ofthe ICU portfolio by including these biomarkers will aid in the early identificationof sepsis patients who may develop septic shock.
机译:尽管在治疗和诊断方面取得了重大进步,败血症仍是死亡和重症监护病房(ICU)入院的主要原因。无法识别出发生败血症性休克的高风险患者会导致败血症负担增加,而快速分子检测目前是帮助确定患者风险和治疗预期的最有希望的途径。这项研究的主要目的是评估影响入住ICU的72名败血症患者的败血症预后的遗传易感性。在脓毒症的关键炎症反应基因中有7个基因多态性,包括肿瘤坏死因子-α,白细胞介素(IL)-1β,IL-10,IL-8,Toll样受体4,CXCR1和CXCR2。主要发现表明,与杂合子相比,IL-10 rs1800896中主要A等位基因纯合的患者发生败血性休克的机会几乎高五倍。同样,选定的临床特征和CXCR2 rs1126579单核苷酸多态性可调节败血性休克易感性,而不会影响生存。这些数据支持分子检测对改善败血症预后模型具有临床实用性的假设。因此,丰富通过包含这些生物标记物的ICU产品组合将有助于早期识别败血症患者可能会发展为败血性休克。

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