胎盘糖皮质激素反应基因甲基化在孕晚期妊娠相关焦虑与胎儿出生结局关联中的作用  

The role of methylation of placental glucocorticoid response gene in the association between pregnancy-related anxiety in the third trimester and birth outcomes

作　　者：刘慧 朱贝贝 陶芳标[1] 邵珊珊 Liu Hui;Zhu Beibei;Tao Fangbiao;Shao Shanshan(Department of Maternal,Child and Adolescent Health,School of Public Health,Anhui Medical University/Key Laboratory of Population Health Across Life Cycle,Ministry of Education of the People′s Republic of China/Anhui Province Key Laboratory of Population Health and Aristogenics,Hefei 230032,China)

机构地区：[1]安徽医科大学公共卫生学院儿少卫生与妇幼保健学系、出生人口健康教育部重点实验室、人口健康与优生安徽省重点实验室,合肥230032

出　　处：《中华预防医学杂志》2023年第2期208-214,共7页Chinese Journal of Preventive Medicine

基　　金：国家自然科学基金(82273638,81803248)。

摘　　要：目的探讨胎盘糖皮质激素反应基因甲基化在孕晚期妊娠相关焦虑与出生结局关联中的作用。方法采用前瞻性队列研究设计,以马鞍山优生优育队列中的单胎活产儿及其母亲为研究对象,采用《妊娠相关焦虑量表》评价母亲孕晚期妊娠相关焦虑症状;从医疗记录中获得新生儿出生结局信息;选取焦虑组和对照组各300个胎盘组织,采用MethylTarget法检测其中FKBP5、NR3C1和HSD11B2基因启动子区的甲基化水平。采用探索性因子分析法提取甲基化因子;采用线性回归或logistic回归模型分析孕晚期妊娠相关焦虑、甲基化因子及出生结局之间的关联;采用Process程序分析甲基化因子在孕晚期妊娠相关焦虑与出生结局关联中的中介作用。结果共纳入2833对单胎活产孕妇及胎儿,母亲年龄为(26.60±3.60)岁。调整混杂因素后,孕晚期妊娠相关焦虑增加小于胎龄儿的发生风险(OR=1.32,95%CI:1.00~1.74)。共提取5个甲基化因子,其中因子5负载了FKBP5 CpGs 18~21;孕晚期妊娠相关焦虑与因子5呈负相关(β=-0.24,95%CI:-0.44~-0.05);因子5与出生胎龄呈正相关(β=0.17,95%CI:0.06~0.27);此外,因子2(β=0.02,95%CI:0.00~0.04)和因子3(β=0.03,95%CI:0.01~0.05)与产后5 min新生儿评分呈正相关。未发现甲基化因子在孕晚期妊娠相关焦虑与出生结局关联中的中介作用。结论孕晚期妊娠相关焦虑可能降低胎盘组织中FKBP5 CpGs 18~21的甲基化水平并与小于胎龄儿的发生风险相关联。Objective To investigate the role of methylation of placental glucocorticoid response gene in the association between pregnancy-related anxiety in the third trimester and birth outcomes.Methods Based on a prospective cohort study,singleton live births and their mothers from the Ma′anshan Birth Cohort Study(MABC)were included as participants in this study.The maternal pregnancy-related anxiety symptoms in the third trimester of pregnancy were evaluated by using the Pregnancy-related Anxiety Questionnaire.The neonatal birth outcomes were collected from medical records.The placental tissues from 300 pregnant women with pregnancy-related anxiety and 300 without pregnancy-related anxiety were collected to detect the methylation of FKBP5,NR3C1 and HSD11B2 genes using the Methyl Target approach.The methylation factors were extracted by exploratory factor analysis.Linear regression or logistic regression models were used to analyze the association between pregnancy-related anxiety in the third trimester,methylation factor scores,and birth outcomes.The mediating role of methylation factors in the association between pregnancy-related anxiety in the third trimester and birth outcomes was analyzed by using the Process procedure.Results The mean age of 2833 pregnant women was(26.60±3.60)years old.After adjusting for confounding factors,pregnancy-related anxiety in the third trimester increased the risk of small-for-gestational-age(OR=1.32,95%CI:1.00-1.74).A total of 5 methylation factors were extracted,and the factor 5 was loaded with FKBP5 CpGs 18-21.Pregnancy-related anxiety in the third trimester was negatively correlated with the factor 5(β=-0.24,95%CI:-0.44--0.05).The factor 5 was positively correlated with the gestational age(β=0.17,95%CI:0.06-0.27).In addition,the factor 2(β=0.02,95%CI:0.00-0.04)and factor 3(β=0.03,95%CI:0.01-0.05)were positively correlated with 5-min Apgar score after delivery.However,this study did not found the mediating role of the scores of the factor characterized by FKBP5 in the relation

关 键 词：焦虑 糖皮质激素 甲基化 出生结局 队列研究 

分 类 号：R715.3[医药卫生—妇产科学]