糖皮质激素受体基因NR3C1 rs10052957位点与环境交互作用增加自杀风险  

Interaction between rs10052957 polymorphism of glucocorticoid receptor gene and environmental factors increases the risk of suicide:a study of 66 cases

作　　者：周艳华 陆奕彬 瞿铭 黄缤慧 张琳娜 邱小英 褚成静 ZHOU Yanhua;LU Yibin;QU Ming;HUANG Binhui;ZHANG Linna;QIU Xiaoying;CHU Chengjing(Faculty of Psychology,College of Humanities and Management,Guangdong Medical University,Dongguan,Guangdong Province,523808;Department of Psychiatry,Dongguan Seventh People’s Hospital,Dongguan,Guangdong Province,523000;Department of Psychiatry,Kuitun Hospital of Ili Kazakh Autonomous Prefecture,Kuitun,Xinjiang Uygur Autonomous Region,833200;Faculty of Grammar,Guangdong Polytechnic Institute,Guangzhou,Guangdong Province,510091;Department of Psychiatry,Brain Hospital Affiliated to Guangzhou Medical University,Guangzhou,Guangdong Province,510370,China)

机构地区：[1]广东医科大学人文管理学院应用心理学系,广东东莞523808 [2]东莞市第七人民医院精神科,广东东莞523000 [3]伊犁哈萨克自治州奎屯医院精神卫生科,新疆奎屯833200 [4]广东理工职业学院文法系,广州510091 [5]广州医科大学附属脑科医院精神科,广州510370

出　　处：《陆军军医大学学报》2023年第12期1354-1362,共9页Journal of Army Medical University

基　　金：国家自然科学基金青年科学基金(81101021)。

摘　　要：目的探讨下丘脑-垂体-肾上腺轴(hypothalamic-pituitary-adrenal axis,HPA)相关基因促肾上腺皮质激素释放激素受体II(corticotropin-releasing hormone receptor 2,CRHR2)、FK506结合蛋白(FK506 binding protein 5,FKBP5)及糖皮质激素受体基因(glucocorticoid receptor gene,NR3C1)多态性和环境交互作用与自杀未遂行为之间的关系。方法自2017年3月至2018年9月选取广东医科大学附属医院精神心理科、东莞市第七人民医院精神科以及新疆奎屯市伊犁州奎屯医院医院精神卫生科门诊因自杀未遂就诊的抑郁症患者66例(病例组),年龄(32.2±16.7)岁,其中男性30名,女性36名,同期自广东医科大学附属医院健康体检中心选取49名无亲缘关系的健康者(对照组),年龄(32.7±11.0)岁,男性23名,女性26名。采用Snapshot技术对目的基因单核苷酸多态性(single nucleotide polymorphism,SNP)位点进行分型。生活事件量表(life event scale,LES)评估过去1年的生活压力。特里尔社会应激试验(trier social stress test,TSST)评估HPA轴的反应性。使用多因子降维法(multifactor dimensionality reduction,MDR)软件分析基因、生活事件及HPA轴反应性的交互作用。结果病例组LES总分[(30.47±27.22)分]高于对照组[(7.80±10.14)分,P<0.001]。病例组HPA轴反应性低于对照组,差异有统计学意义(P<0.001);两组NR3C1基因的多态性位点rs9324924、rs10052957,FKBP5基因的多态性位点rs3800373、rs9296158,CRHR2基因多态性位点rs3779250的基因型频率和等位基因型频率分布差异均无统计学意义。MDR分析结果显示,最佳交互模型为NR3C1基因rs10052957位点、HPA轴反应性、生活事件形成的三阶模型,检验样本准确度最高为0.8837,模型具有统计学意义(P=0.0098)。结论NR3C1基因rs10052957位点-HPA轴反应性-生活事件交互作用增加了自杀行为的风险。Objective To investigate the interactions of the polymorphisms of hypothalamic-pituitary-adrenal(HPA)axis related genes,corticotropin-releasing hormone receptor II(CRHR2),FK506 binding protein 5(FKBP5),and glucocorticoid receptor(NR3C1)with environmental factors,and their association with suicide attempts.MethodsA total of 66 depressed patients(32.2±16.7 years old,30 males and 36 females,case group)who seek medical advice due to attempted suicide were recruited from the psychiatry departments of the Affiliated Hospital of Guangdong Medical University,Dongguan Seventh People’s Hospital and Kuitun Hospital of Ili Kazakh Autonomous Prefecture during March 2017 to September 2018.Forty-nine unrelated healthy individuals(32.7±11.0 years old,23 males and 26 females,control group)were selected from the Health Screening Centre of the Affiliated Hospital of Guangdong Medical University during the same period.Snapshot genotyping was used to test the single nucleotide polymorphism(SNP)loci of the target genes.Life event scale(LES)was used to assess life stress of individuals over the past year.Trier social stress test(TSST)was employed to evaluate HPA axis reactivity.Mmultifactor dimensionality reduction(MDR)analysis was adopted to analyze the interactions among genes,life events and HPA axis reactivity.ResultsThe total LES score was significantly higher(30.47±27.22 vs 7.80±10.14,P<0.001),but the HPA axis reactivity was obviously lower in the case group than the control group(P<0.001).There were no statistical differences in genotype frequencies and allele frequencies between the 2 groups at 5 SNPs(NR3C1:rs9324924 and rs10052957;FKBP5:rs3800373 and rs9296158;CRHR2:rs3779250).MDR analysis indicated that the best interaction model was the third-order model constructed by NR3C1 rs10052957 polymorphism,life events and HPA axis reactivity,with the highest accuracy of 0.8837 for sample test(P=0.0098).ConclusionThe interaction of NR3C1 rs10052957 polymorphism,HPA axis reactivity and life events can increase the risk of suicid

关 键 词：自杀未遂 HPA轴基因 HPA轴反应性 生活事件 

分 类 号：R195.1[医药卫生—卫生统计学] R394.3[医药卫生—卫生事业管理] R749.4[医药卫生—公共卫生与预防医学]