BDNF多态性在氟暴露与儿童ACTH/CORT关联中的作用  

The role of BDNF polymorphism in the association between fluoride exposure and ACTH/CORT in children

作　　者：李娜 冯子臣 周郭育 王安琪 丁丽敏 余方方 巴月 Li Na;Feng Zichen;Zhou Guoyu;Wang Anqi;Ding Limin;Yu Fangfang;Ba Yue(Dietary Center,Zhengzhou Health Vocational College,Zhengzhou 450001,China;Department of Environmental Health,School of Public Health,Zhengzhou University,Zhengzhou 450001,China;Center for Disease Control and Prevention of Henan Province,Zhengzhou 450001,China)

机构地区：[1]郑州卫生健康职业学院膳食中心,郑州450001 [2]郑州大学公共卫生学院环境卫生学教研室,郑州450001 [3]河南省疾病预防控制中心,郑州450001

出　　处：《中华地方病学杂志》2024年第9期689-697,共9页Chinese Journal of Endemiology

基　　金：国家自然科学基金(81972981、82003401)

摘　　要：目的探讨豫东农村儿童氟暴露与促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)和皮质醇(cortisol,CORT)的关系,揭示脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)基因多态性在其中的修饰效应。方法采用整群抽样方法,于河南省通许县4所小学招募7~12岁儿童463名(男童245名、女童218名),对其进行问卷调查、体格检查以及晨尿、空腹静脉血采集。分别应用氟离子选择电极法和苦味酸法测定尿氟及尿肌酐浓度;结合全自动生化分析仪测定血清ACTH及CORT水平;采用定制的48-Plex SNPscan^(TM)试剂盒对BDNF基因单核苷酸多态性位点进行基因分型。使用多元线性回归分析尿氟浓度与儿童血清ACTH或CORT水平的关系;同时建立尿氟浓度与BDNF基因多态性的交互项,使用多元线性回归分析单位点基因多态性与环境对儿童血清ACTH或CORT水平的交互作用。结果尿氟浓度每升高1 mg/L,女童血清ACTH水平增加1.98 pg/ml[95%置信区间(CI):0.71,3.24;P=0.002]、男童血清CORT水平降低37.48 ng/ml(95%CI:-63.99,-10.97;P=0.006)。无论是否分层分析,携带rs6484320位点TA基因型者尿氟浓度均与血清ACTH水平呈正相关(均β>0,均P<0.05);携带rs7103873位点CC基因型的总人群和男童尿氟浓度均与血清ACTH水平呈正相关(均β>0,均P<0.05);携带rs12291186位点AA基因型的女童尿氟浓度与血清ACTH、CORT水平均呈正相关(均β>0,均P<0.05)。交互作用分析显示,总人群和男童尿氟浓度分别与rs6484320、rs7103873位点多态性对血清ACTH水平均有交互作用(均P_(交互)<0.1);女童尿氟浓度与rs12291186位点多态性对血清CORT水平有交互作用(P_(交互)=0.035)。结论尿氟浓度与女童血清ACTH水平升高及男童血清CORT水平降低有关;BDNF基因多态性可修饰氟暴露与儿童血清ACTH或CORT水平的关联,且修饰效应存在性别差异。Objective To study the relationship between fluoride exposure and adrenocorticotropic hormone(ACTH)/cortisol(CORT)in rural children in eastern Henan,and to reveal the modifying effect of brain-derived neurotrophic factor(BDNF)gene polymorphism.Methods A total of 463 children aged 7-12(245 boys and 218 girls)from 4 primary schools in Tongxu County,Henan Province were recruited by a cluster sampling method for questionnaire survey,physical examination,and collection of morning urine and fasting venous blood.The concentrations of urinary fluoride and creatinine were determined by a fluoride ion selective electrode method and picric acid method,respectively.Serum ACTH and CORT levels were determined with a fully automated biochemical analyzer,and the genotyping of BDNF gene loci of single nucleotide polymorphism was conducted by a customized 48-Plex SNPscanTM reagent kit.Besides,the relationships between urinary fluoride concentrations and serum ACTH/CORT levels in children were analyzed by multiple linear regression models.The interaction term between urinary fluoride concentration and BDNF gene polymorphism was established,and the interaction between unit point gene polymorphism and environment on serum ACTH or CORT levels of children was analyzed by multiple linear regression.Results For every 1 mg/L increase in urinary fluoride concentration,serum ACTH level in girls increased by 1.98 pg/ml[95%confidence interval(CI):0.71,3.24;P=0.002],while serum CORT level in boys decreased by 37.48 ng/ml(95%CI:-63.99,-10.97;P=0.006).Regardless of stratified analysis,the urinary fluoride concentration of individuals carrying the TA genotype at the rs6484320 locus was positively correlated with serum ACTH level(β>0,P<0.05);in addition,there was a positive correlation between urinary fluoride concentration and serum ACTH level in the total population and boys carrying the CC genotype of rs7103873 locus(β>0,P<0.05);and the serum ACTH and CORT levels in girls carrying the AA genotype of rs12291186 locus were positively correlated

关 键 词：氟 儿童 脑源性神经营养因子 单核苷酸多态性 促肾上腺皮质激素 皮质醇 

分 类 号：R179[医药卫生—妇幼卫生保健] R725.9[医药卫生—公共卫生与预防医学]