糖皮质激素受体和促肾上腺皮质激素受体基因多态性与应激的关系  

Associations of GR and ACTHR gene polymorphisms with quantitative trait of strain

作　　者：连玉龙[1] 李富业[1] 王磊[1] 王茜[1] 宁丽[1] 张晨[1] 刘继文[1] 

机构地区：[1]新疆医科大学公共卫生学院,乌鲁木齐830011

出　　处：《中华劳动卫生职业病杂志》2011年第12期902-907,共6页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金资助项目（30833906）;新疆维吾尔自治区教育厅青年科研启动基金（XJE-DU009S50）;新疆维吾尔自治区自然科学基金资助项目（2010211A32）

摘　　要：目的探讨糖皮质激素受体（GR）、促肾上腺皮质激素受体（ACTHR）基因多态性与应激反应的关联。方法采用单纯随机抽样的方法抽取200名汉族无器质性患者的中小学教师，采用聚合酶链反应一限制性片段长度多态性分析（PCR．RFLP）法测定GR基因GRA5556G、A5556G、GAGG4534／4536AAAG以及ACTHR基因pmmoterT．2C多态性位点，应用应激相关工作分析工具6．0、生活事件量表测定应激因素，应用工作应激反应问卷（JSS）、症状自评量表（SCL-90）问卷、总体幸福感量表（GWB）测试心理应激反应，血清中皮质醇、促肾上腺皮质激素（ACTH）水平及神经行为功能测试反映生理应激反应，应用综合性工作能力指数（CWAI）量表测试工作能力，然后利用结构方程模型综合评价应激反应。结果GRA5556GG／A基因型个体心理应激反应得分、血清中皮质醇水平高于A，A基因型个体，而工作能力得分、ACTH水平低于～A基因型个体，差异有统计学意义（P〈0．01）。GAGG4534／4536AAAGA／G基因型个体心理应激反应得分、皮质醇水平高于G／G基因型个体，而反应灵敏度和运动灵敏度低于G／G基因型个体，差异有统计学意义（P〈0．01）。GRC6294GC／C和C／G基因型个体皮质醇水平低于G／G基因型个体，差异有统计学意义（P〈0．01）。ACTHRpromoter T-2CT仃基因型个体ACTH水平低于C／C和C／T基因型个体，差异有统计学意义（P〈0．01）.与野生型相比，GRA5556G与GRGAGG4534／4536AAAG基因变异型对皮质醇水平水平呈正交互作用（βs=0．543，P〈0．01），而对SCL-90的水平有负交互作用（βs=-0．374，P〈0．01）。GRA5556G与GRC6294G基因对皮质醇水平呈正交互作用（βs=0．465，19〈0．05）。GR、ACTHR基因变异对于心理应激反应、生理应激反应、工作能力降低是促进因素（βs值分别为0．62，0．43，-0．74，P〈0．01），工作应激因素Objective To explore association between GR and ACTHR gene polymorphisms and quantitative trait of stress in Chinese Han population. Methods Four polymorphic markers （GRA5556G, A5556G, GAGG4534/4536AAAG, promoter T-2C） in GR gene and ACTHR gene were genotyped with PCR-RLFP in 200 healthy Hans. ISTA6.0 and life event stressor questionnaire was used to assess stressors. JSS, SCL-90 and GWB questionnaires were used to quantify the phenotypes of stress. Blood cortical and ACTH levels, and ner- vous behavior function were measured to assess Physiological strain. CWAI questionnaire was used to assess work ability. Then strain was assessed with Structural equation modeling （SEM）. Results The subjects with GR A5556G genotype （G/A） showed significantly higher plasma cortisol levels, higher psychological stress scores, lower work ability scores and lower plasma ACTH levels compared with the subjects with wild-type （P〈0.01）. Psychological stress scores and plasma cortisol levels in the subjects with GR GAGG4534/4536AAAG AG genotype were significantly higher than those in the subjects with wild-type, but the reaction and action sensitivity in the subjects with GR GAGG4534/4536AAAG AG genotype were significantly lower than those in ones with wild-type （P〈0.01）. The ACTH level in the subjects with ACTHR promoter T-2C T/T genotype was significantly lower than that in ones with C/C and C/T genotype （P〈0.01）. Interaction of GRA5556G and GG4534/ 4536AAAG with plasma cortisol was positively associated （βs=0.543,P〈0.01）,butwithSCL-90scorewasnega- tively associated （βs=-0.374, P〈0.01 ）. Interaction of GRA5556G and GGC6294G with plasma cortisol was correlated （βs=0.465, P〈0.05）. While GR and ACTHR gene variants are the risk factors for psychological strain, physiological strain and decreased work ability （βs are 0.62,0.43, -0.74, respectively （P〈0.01）. While scarce social support, job stressors, negative life stressors and dangerous individual characters are the risk factors

关 键 词：应激 多态性 单核苷酸 受体 糖皮质激素 受体 促肾上腺皮质激素 

分 类 号：R341[医药卫生—基础医学]