间隙性连接蛋白37基因多态性与重型颅脑损伤后脓毒症易感性的关联性

Association of polymorphism of connexin 37 gene with the susceptibility to sepsis after severe head injury

目的分析间隙性连接蛋白37(Cx37)基因多态性与重型颅脑损伤后脓毒症易感性的关联性。方法选择天津市北辰区中医医院2017年5月-2020年5月收治为重型颅脑损伤后发生脓毒症患者80例设为研究组,另选择同期医院收治的颅脑损伤但未发生脓毒症患者76例为对照组。提取全血标本中DNA,采用聚合酶链式扩增反应(PCR)对DNA模板中目标序列进行扩增并进行测序,确定Cx37基因rs1764390位点基因分型。分离为单个核淋巴细胞(PBMCs)后,采用实时荧光定量聚合酶链式反应(RT-PCR)检测Cx37基因mRNA在患者PBMCs上的表达水平。结果研究组患者Cx37基因rs2232618位点AG、GG基因型、G等位基因频率分别为41.25%、23.75%、44.38%均高于对照组,AA基因型频率为35.00%低于对照组(P<0.05);Cx37基因rs1764390位点AG型患脓毒症的风险是AA型的1.819倍,GG型患脓毒症的风险是AA型的2.532倍,AG/GG型患脓毒症的风险是AA型的2.349倍。研究组Cx37基因rs1764390位点携带不同基因型患者Cx37 mRNA水平、14 d病死率差异有统计学意义(P<0.05),GG型患者病死率最高,其余各结局指标(住院时间、住ICU时间、机械通气时间)研究组不同基因型间差异无统计学意义。结论Cx37基因rs2232618位点单核苷酸多态性与本地区居民重型颅脑损伤后脓毒症易感性有关,其中G等位基因为易感基因,携带GG型患者病死率较高。

OBJECTIVE To analyze the association between gene polymorphism of connexin 37(connexin 37,Cx37)and susceptibility to sepsis after severe head injury.METHODS Tootally 80 patients with sepsis after severe head injury admitted at the Tianjin Beichen District Traditional Chinese Medicine Hospital from May 2017 to May 2020 were selected as the study group,another 76 patients with craniocerebral injury but no sepsis who were admitted to the hospital during the same period were selected as the control group.The DNA in the whole blood sample was extracted,the target sequence in the DNA template was amplified and sequenced by polymerase chain amplification reaction(PCR),and the genotype of the Cx37 gene rs1764390 locus was determined.After separation of mononuclear lymphocytes(PBMCs),real-time fluorescent quantitative polymerase chain reaction(RT-PCR)was used to detect the expression level of Cx37 gene mRNA on the patient′s PBMCs.RESULTS The frequencies of AG,GG genotype,and G alleles at Cx37 gene rs2232618 in the study group were 41.25%,23.75%,and 44.38%,respectively,significanttly higher than those of the control group,and the frequency of AA genotype was 35.00%,significanttly lower than that of the control group(P<0.05)).The risk of sepsis of AG type at rs1764390 site of Cx37 gene was 1.819 times of that of type AA,the risk of sepsis of GG was 2.532 times that of type AA,the risk of sepsis of AG/GG was 2.349 times of that of type AA.The Cx37 gene rs1764390 locus of the Cx37 gene in the study group carried different genotypes in the Cx37 mRNA level and the 14-day case fatality rate were significant(P<0.05).The case fatality rate of patients with GG type was the highest.There was no significant difference between the study groups in the time of mechanical ventilation.CONCLUSION The single nucleotide polymorphism at rs2232618 of the Cx37 gene was related to the susceptibility of local residents to sepsis after severe head injury,among which,the G allele was a susceptible gene,and the mortality rate of patients with GG type was higher.