汉族脓毒症患者转录因子NF-E2相关因子2基因启动子-617C/A单核苷酸多态性的研究

An association between NF-E2-related factor 2-617C/A gene polymorphisms and sepsis in Chinese Han population

目的 探讨转录因子NF-E2相关因子2（NRF2）启动子-617C/A多态性与脓毒症的易感性、严重程度及预后的关系.方法 应用DNA直接测序法检测浙江温州地区174例汉族脓毒症患者和203例健康体检者的NRF2启动子-617位点多态性,分析NRF2-617C/A与脓毒症易感性、严重程度及预后的关系.结果 （1）脓毒症者NRF2-617位点突变率（CA＋ AA）明显高于健康体检者（59.2％比46.3％;P =0.012）.（2）一般脓毒症者和严重脓毒症者NRF2-617基因型（CA＋ AA）分布差异有统计学意义（47.5％比65.5％;P=0.033）,但脓毒症休克者与无休克者（61.8％比57.1％;P=0.221）、脓毒症死亡者与存活者间无明显差别（56.8％比66.7％;P=0.258）.（3）非条件logistic回归分析显示：NRF2-617位点C→A突变与脓毒症易感性（OR=1.584,95％ CI1.025～2.447,P=0.038）及发生严重脓毒症（OR=0.453,95％ CI0.233～0.878,P=0.019）有关.结论 NRF2-617位点C→A突变与脓毒症易感性及发生严重脓毒症相关,但与脓毒症是否发生休克及预后无关.

Objective To investigate the association between the single nucleotide polymorphisms （SNPs） in NF-E2-related factor 2-617 （NRF2-617） promoter region with the susceptibility to the risk of sepsis.Methods In this case-control association study,203 healthy controls and 174 patients with sepsis in Wenzhou Han population were enrolled and genotyped by DNA direct sequencing.Results （1） The （CA ＋ AA） genotype frequency was significantly higher in the sepsis group than in the control group（59.2% vs 46.3 %,P =0.012）.（2） Compared with the general sepsis group,higher （CA ＋ AA） genotype frequency was found in the severe sepsis group（47.5% vs 65.5%,P =0.033）.However,no significant difference was shown in the（CA ＋ AA）genotype frequency between the shock group and the non-shock group as well as between the death group and the non-death group （61.8% vs 57.1%,P =0.221 ; 56.8% vs 66.7%,P =0.258）.（3）The unconditional logistic regression analysis showed that the mutation of C to A at the gene promoter locus of Nrf2-617 was associated with the increased onset risk of sepsis （OR =1.584,95% CI 1.025-2.447,P =0.038） and the severity of sepsis （OR =0.453,95% CI 0.233-0.878,P =0.019）.Conclusion The mutation of C to A at the gene promoter locus of Nrf2-617 may increase the onset risk of sepsis and organ failure in sepsis patients,while not associated with the incidence of shock and the prognosis of sepsis.