糖皮质激素受体基因多态性与脓毒症临床转归的相关性研究

Association of polymorphisms in glucocorticoid receptor with outcome of sepsis in a Chinese Han population

目的 探讨华东汉族人群糖皮质激素受体（glucocorticoid receptor,GR）基因多态性与脓毒症临床转归的相关性。方法 共募集脓毒症患者194例。以连接酶检测反应（ligase detection reaction,LDR）技术对GR基因中的15个单核苷酸多态性（single nucleotide polymorphism,SNP）位点进行基因分型。非条件Logistic回归,校正年龄、性别、吸烟、饮酒、APACHEⅡ评分后,在不同遗传模式下分析各基因型与脓毒症临床转归（器官功能障碍、休克、死亡）的相关性。结果 rs9324924 GT/TT携带者与GG携带者相比较,可能降低重度器官功能障碍风险（OR[95%CI]=0.39[0.16~0.99],P=0.047）;rs4912905CG/CC携带者与GG携带者相比较,发生重度器官功能障碍风险增加（OR[95%CI]=2.53（0.99~6.50）,P=0.047）;rs9324921 CA/AA携带者与发生脓毒性休克的风险是CC携带者的2.47倍（OR[95%CI]=2.47（1.04~5.84）,P=0.038）。未发现与脓毒症死亡相关的位点。结论 GR基因单核苷酸多态性可能与华东汉族人群脓毒症后器官功能障碍和休克发生相关。

Objective To explore the association of glucocorticoid receptor （ GR） gene polymorphisms with outcome of sepsis in Eastern China population. Methods Total of 15 single nucleotide polymorphisms （ SNPs） were classified by genotype in 194 septic patients using LDR technology. Unconditioned logistic regression analysis was used to explore the association of GR gene polymorphisms with outcome （ organ dysfunction/shock/death） of sepsis after adjusting for age, sex, smoking and drinking status and APACHEⅡscore. Results Compared with GG genotype, the rs9324924GT/TT reduced severity of organ dysfunction with OR value of 0.39（95%CI：0.16-0.99, P=0.047） . The rs4912905 CG/CC genotype increased the risk of severe organ dysfunction compare with GG genotype （OR[95%CI]= 2.47[1.04-5.84], P=0.038）. The CA/AA genotype of rs9324921 polymorphism were significantly overrepresented among septic shock patients compared with controls （OR [95%CI]= 2.47[1.04-5.84], P=0.038）. However, there were no associa-tions between polymorphisms of GR gene and death of sepsis. Conclusion Genetic polymorphisms in GR gene are thought to associate with severity of organ failure and shock after sepsis.