脓毒症患儿载脂蛋白E基因多态性分布研究

The correlation between the apolipoprotein E genetic polymorphisms and sepsis in children

目的研究我国儿童载脂蛋白E基因多态性与脓毒症的相关性。方法将2011年3月至2012年6月临床诊断为脓毒症患儿纳入研究组，将在复旦大学附属儿科医院就诊的健康体检儿童纳入对照组。所有研究对象均采用高通量熔解曲线分析技术进行了载脂蛋白E基因分型。应用SPSS 16.0版本进行统计分析。组间年龄比较采用Mann-Whitney U秩和检验，组间性别和基因频率比较采用卡方检验，混杂因素采用多因素非条件Logistic回归分析，Hardy-Weinberg平衡采用χ2检验进行分析，以P〈0.05为差异具有统计学意义。结果2011年3月至2012年6月期间，共收集研究对象285例，其中脓毒症组88例，15例合并中枢神经系统感染。对照组197例。共检测到4种载脂蛋白E基因型：ε3/ε3、ε2/ε3、ε3/ε4、ε2/ε4。脓毒症组与对照组的基因型分布分别为64.4%、73.1%（ε3/ε3）；16.8%、10.7%（ε2/ε3）；18.8%、14.7%（ε3/ε4）；0%、1.5%（ε2/ε4），脓毒症组ε3/ε3的基因型分布低于对照组（P=0.047，1－β = 0.334，OR=0.585，校正OR=0.559）。伴发中枢感染的脓毒症患者ε3/ε3基因型分布为33.3%、明显低于无中枢感染的脓毒症患者（67.1%）（P=0.014，1－β = 0.685，OR=0.245，校正OR=0.275）。结论载脂蛋白E基因多态性与儿童脓毒症发生及其中枢感染合并症相关，ε3/ε3基因型对脓毒症及中枢感染合并症的易感性明显低于其他几种基因型。

ObjectiveTo study the correlation between apolipoprotein E （APOE） genetic polymorphisms and sepsis in Chinese children.MethodsThe inpatients suffered with sepsis were enrolled as septic group and the healthy children from child health division were enrolled as control group. The study of APOE genotypes were carried out by polymerase chain reactions followed a high-resolution melting curve analysis. SPSS 16.0 statistical software was used for data analysis. Mann-Whitney U test was used to compare the age between the groups. Hardy-Weinberg equilibrium was tested using the Pearson χ2 -test. The χ2 -test was used to compare gender and the genotype distribution between the groups. The odd ratio （OR） was calculated together with its 95% confidence interval （CI）. Potential confounding effects of variables were corrected using a multivariate unconditional logistic regression model. All statistical tests were two-sided and P 〈 0.05 indicates statistically significance.ResultsAmong a total of 285 children collected from March 2011 to June 2012, there were 88 patients with sepsis and 197 healthy children. In the septic group, 15 septic patients were complicated with central nervous system infection. Four apolipoprotein E genotypes were identified to be ε3/ε3, ε2/ε3, ε3/ε4, and ε2/ε4. The percentage of each genotype found in patients of the septic group and the control group was 64.4% vs. 73.1% （ε3/ε3）; 16.8% vs. 10.7% （ε2/ε3）; 18.8% vs. 14.7% （ε3/ε4）; 0% vs. 1.5% （ε2/ε4）, respectively. The number of patients with the genotype ε3/ε3 among septic patients was significantly lower than that among the control individuals （P = 0.047, 1-β = 0.334, OR = 0.585, adjusted OR = 0.559）. The number of patients with the genotype ε3/ε3 among the septic patients with central nervous system infection was 33.3%, which was also significantly lower than that among the septic patients without CNS infection （67.1%）. （P = 0.014, 1-β = 0.685, OR = 0.245, adjusted OR = 0.275）.ConclusionsApolipoprotein E genetic polymorphisms were associated with the occurrence of sepsis and central nervous system complications in children. The susceptibility of children with genotype ε3/ε3 to sepsis and central nerve system infection complications is significantly lower than that of children with other genotypes.