重症监护病房脓毒症患者热休克蛋白70基因多态性与临床结局的关联
Association between heat shock protein 70 gene polymorphisms and clinical outcomes in intensive care unit patients with sepsis.
作者信息
Ramakrishna Kartik, Pugazhendhi Srinivasan, Kabeerdoss Jayakanthan, Peter John Victor
机构信息
Department of Intensive Care, Wellcome Trust Research Laboratory, Christian Medical College, Vellore, Tamil Nadu, India ; Department of Internal Medicine, Unity Health System, Rochester, NY 14626, USA ; Department of Gastrointestinal Sciences, Wellcome Trust Research Laboratory, Christian Medical College, Vellore, Tamil Nadu, India.
Department of Gastrointestinal Sciences, Wellcome Trust Research Laboratory, Christian Medical College, Vellore, Tamil Nadu, India.
出版信息
Indian J Crit Care Med. 2014 Apr;18(4):205-11. doi: 10.4103/0972-5229.130571.
OBJECTIVE
The objective of the following study is to evaluate the associations between single nucleotide polymorphisms (SNPs) in the Heat Shock Protein 70 (HSP70) gene, gene expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) and medical intensive care unit (MICU) stay and organ failure in sepsis.
MATERIALS AND METHODS
MICU patients with sepsis were genotyped for rs1061581, rs2227956, rs1008438 and rs1043618 polymorphisms in HSP70 gene using polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis or allele-specific PCR. Messenger ribonucleic acid (mRNA) expression of IL-6 and TNF-α were quantitated in peripheral blood lymphocytes. Outcomes were recorded.
RESULTS
108 patients (48 male) aged 40.7 ± 16.0 (mean ± standard deviation) years included H1N1 infection (36), scrub typhus (29) and urosepsis (12). Seventy-one (65.7%) had dysfunction of three or more organ systems, 66 patients (61.1%) were treated by mechanical ventilation, 21 (19.4%) needed dialysis. ICU stay was 9.3 ± 7.3 days. Mortality was 38.9%. One or more SNPs were noted in 101/108 (93.5%) and organ failure was noted in only 1/7 patients without a single SNP. The A allelotypes of rs1061581 and rs1008438 were associated with hematological dysfunction (P = 0.03 and 0.07) and longer ICU stay (P = 0.05 and 0.04), whereas IL-6 and TNF-α mRNA levels were associated with central nervous system dysfunction.
CONCLUSIONS
HSP70 genotypes may determine some adverse outcomes in patients with sepsis.
目的
以下研究的目的是评估热休克蛋白70（HSP70）基因中的单核苷酸多态性（SNP）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的基因表达与脓毒症患者入住医学重症监护病房（MICU）的时间及器官功能衰竭之间的关联。
材料与方法
采用聚合酶链反应（PCR）-限制性片段长度多态性分析或等位基因特异性PCR，对MICU中脓毒症患者的HSP70基因rs1061581、rs2227956、rs1008438和rs1043618多态性进行基因分型。对外周血淋巴细胞中IL-6和TNF-α的信使核糖核酸（mRNA）表达进行定量分析。记录研究结果。
结果
108例患者（48例男性），年龄40.7±16.0（均值±标准差）岁，包括甲型H1N1感染（36例）、恙虫病（29例）和泌尿道脓毒症（12例）。71例（65.7%）患者存在三个或更多器官系统功能障碍，66例（61.1%）患者接受了机械通气治疗，21例（19.4%）患者需要透析治疗。入住ICU的时间为9.3±7.3天。死亡率为38.9%。101/108（93.5%）患者存在一个或多个SNP，而在无单个SNP的患者中，仅1/7出现器官功能衰竭。rs1061581和rs1008438的A等位基因与血液系统功能障碍（P = 0.03和0.07）及更长的ICU住院时间（P = 0.05和0.04）相关，而IL-6和TNF-α的mRNA水平与中枢神经系统功能障碍相关。
结论
HSP70基因分型可能决定脓毒症患者的某些不良预后。
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