核受体FXR基因多态性与肺炎脓毒症临床转归的相关性研究  

Association of the farnesoid X receptor gene polymorphisms with clinical outcomes of sepsis caused by pneumonia

作　　者：朱小蔚 黄方[2] 方放[2] 郭蕾[2] 杨晨 万文辉[2] 刘瑜[2] ZHU Xiao-wei. Health Care Office; HUANG Fang, FANG Fang, GUO Lei, YANG Chen, WAN Wen-hui, LIU Yu.(Department of Geriatrics, Nanjing General Hospital of PLA, Nanjing 210002, Chin)

机构地区：[1]中国人民解放军南京军区南京总医院保健科,江苏省南京市210002 [2]中国人民解放军南京军区南京总医院干部病房,江苏省南京市210002

出　　处：《实用老年医学》2018年第7期653-657,共5页Practical Geriatrics

基　　金：国家自然科学基金(81701890);全军保健专项科研课题(13BJZ11)

摘　　要：目的探讨汉族人群法尼酯衍生物X受体(FXR)基因多态性与肺炎脓毒症临床转归的相关性。方法共募集肺炎脓毒症病人194例。以改良的多重连接酶检测反应(improved multiplex ligation detection reaction,i MLDR)技术,对FXR基因中11个常见的单核苷酸多态性(single nucleotide polymorphism,SNP)位点进行基因分型。采用非条件Logistic回归分析,校正年龄、性别、吸烟、饮酒、急性生理与慢性健康评分(APACHEⅡ)等因素后,在不同遗传模式下分析各位点基因型与脓毒症临床转归(脓毒性休克、器官功能障碍、死亡)的相关性。结果 rs17030270 GG基因型发生重度器官功能障碍的风险较AA/AA+GA型增高,比值比(odds ratio,OR)和95%置信区间(confidence interval,CI)分别为[7.13(1.83~27.77),P=0.0043和6.98(2.04~23.90),P=0.0018)];rs11110411 CC基因型较TT/TT+CT发生重度器官功能障碍的风险增高,[OR(95%CI)=4.72(1.24~18.00)和4.13(1.50~11.32)];rs35735 TT基因型较GG/GG+GT发生重度器官功能障碍的风险增高[OR(95%CI)=6.52(1.58~26.98),P=0.013和6.50(1.69~25.02),P=0.0063];rs1030454 GG基因型较AA/AA+GA发生重度器官功能障碍的风险降低[OR(95%CI)=0.05(0.01~0.52),P=0.012和0.09(0.01~0.80),P=0.0058],GA+GG较AA发生重度器官功能障碍的风险降低[OR(95%CI)=0.29(0.12~0.72),P=0.0065]。未发现基因多态性位点与脓毒性休克和死亡相关。结论 FXR基因多态性可能与肺炎脓毒症器官功能障碍相关。Objective To explore the association of farnesoid X recepter（FXR） gene polymorphisms with clinical outcomes of sepsis induced by pneumonia. Methods A total of 194 septic patients caused by pneumonia were collected. Improved multiple ligase detection reaction（i MLDR） was performed to test the gene polymorphisms of 11 target single nucleotide polymorphisms（SNPs） of FXR.Unconditioned Logistic regression analysis was used to explore the association of FXR gene polymorphisms with clinical outcomes of sepsis after adjusting for age,sex,smoking,drinking and APACHE Ⅱ scores.Results Compared with AA/AA ＋ GA genotype,GG genotype was associated with increased risk of severe organ dysfunction of septic patients in rs17030270. For rs11110411,CC genotype was related to higher risk of sever organ dysfunction compared with TT/TT＋CT genotype. For rs35735,TT genotype was correlated with higher risk of sever organ dysfunction compared with GG/GG ＋ GT genotype. Compared with AA/AA＋GA genotype,GG genotype was associated with lower risk of severe organ dysfunction in rs1030454. No mutation was correlated with septic shock or death. Conclusions The variations of FXR gene may play a role in organ dysfunction of the patients with sepsis caused by pneumonia.

关 键 词：脓毒症 法尼酯衍生物X受体 单核苷酸多态性 临床转归 

分 类 号：R563.1[医药卫生—呼吸系统]