脑特异性血管发生抑制剂1相关蛋白2基因与中国汉族注意缺陷多动障碍儿童执行功能的关联分析  

Brain-specific angiogenesis inhibitor 1-associated protein 2 gene associates with executive functions in Han Chinese children with attention deficit/hyperactivity disorder

作　　者：李海梅[1] 刘珮 刘宁宁 刘璐[1] 王玉凤[1] 钱秋谨[1] Li Haimei;Liu Pei;Liu Ningning;Liu Lu;Wang Yufeng;Qian Qiujin(Peking University Sixth Hospital,Peking University Institute of Mental Health,the Key Laboratory of Mental Health,Ministry of Health(Peking University),National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital),Beijing 100191,China;Shenzhen Kangning Hospital,Shenzhen Mental Health Center,Shenzhen Clinical Research Center for Mental Disorders,Shenzhen 518020,China)

机构地区：[1]北京大学第六医院、北京大学精神卫生研究所、国家卫生健康委员会精神卫生学重点实验室(北京大学)、国家精神心理疾病临床医学研究中心(北京大学第六医院),北京100191 [2]深圳市康宁医院、深圳市精神卫生中心、深圳市精神心理疾病临床医学研究中心,深圳518020

出　　处：《中华精神科杂志》2024年第11期721-728,共8页Chinese Journal of Psychiatry

基　　金：国家自然科学基金面上项目(81873802,82271575);北京市卫健委第三批研究型病房项目。

摘　　要：目的探讨脑特异性血管发生抑制剂1相关蛋白2(brain-specific angiogenesis inhibitor 1-associated protein 2,BAIAP2)基因多态性与注意缺陷多动障碍(attention deficit/hyperactivity disorder,ADHD)及健康儿童执行功能之间的关联,并进一步探讨这种关联的性别和亚型特异性。方法采用横断面研究,纳入2005年5月至2011年1月于北京大学第六医院门诊就诊的ADHD儿童929例(ADHD组)及2005年1月至2010年1月在北京市中小学就读的健康对照儿童161名(对照组),采用Stroop色词命名测验、Rey复杂图形测验和连线测验评估所有受试者反应抑制、工作记忆及转换功能等执行功能。选择BAIAP2基因4个单核苷酸多态性位点,采用TaqMan^(TM)荧光探针杂交扩增的基因分型技术进行基因型检测。以性别、年龄和智商为协变量,采用协方差分析方法进行2组间执行功能的比较,并探讨BAIAP2基因多态性基因型与ADHD儿童及健康对照儿童执行功能的关联,及ADHD组中这种关联的性别、亚型特异性。结果ADHD组反应抑制功能(F=11.64、26.50,P≤0.001)及转换功能(F=25.68,P<0.001)均较对照组差。对照组中未发现任一BAIAP2基因位点与执行功能关联。在ADHD组中控制性别、年龄、智商后,BAIAP2基因的rs4969239位点与连线测验的转换时间具有统计学意义的关联(B=-17.55,F=7.13,P=0.008),AG+GG等位基因型携带者较AA基因型携带者转换时间长,转换功能较差;rs9901648位点与Stroop色词测验的颜色干扰时具有统计学意义的关联(B=1.82,F=8.84,P=0.003),AA基因型携带者较AG+GG等位基因携带者颜色干扰时更长,反应抑制功能较差。进一步分析显示,rs9901648位点与颜色干扰时的关联仅在男性ADHD儿童中具有统计学意义(F=11.33,P=0.001)。结论BAIAP2基因多态性位点可能与ADHD儿童转换及反应抑制等执行功能受损有关,其中BAIAP2基因多态性位点与反应抑制功能的关联主要存在男性ADHD儿童中。ObjectiveTo investigate the associations between several single nucleotide polymorphisms(SNPs)at BAIAP2 with executive functions in patients with attention deficit/hyperactivity disorder(ADHD)and in healthy control subjects.To investigate if these associations are sex-specific and/or subtype-specific.MethodsA total of 929 Han Chinese youths with DSM-ⅣADHD were recruited from the outpatient department of Peking University Sixth Hospital from May 2005 to January 2011,and 161 unaffected controls were recruited from the primary and secondary schools in Beijing from January 2005 to January 2010.All subjects were rated for the clinical information and executive functions based on laboratory examinations,such as inhibition,working memory,and set shifting.Four SNPs of BAIAP2 were chosen and genotyped using TaqMan^(TM)real-time PCR assays.Analysis of covariance(ANCOVA)were conducted,with gender,age and IQ as covariates,to compare executive functions between children with ADHD and normal controls,and to explore the association of BAIAP2 SNPs with executive functions of ADHD subjects(total samples and sex/subtype stratified samples)and unaffected controls.ResultsCompared to unaffected controls,children with ADHD performed significantly worse in inhibition(F=11.64,26.50,P≤0.001)and set shifting(F=25.68,P<0.001).In unaffected controls,there was no correlation between any BAIAP2 SNPs and executive functions.In ADHD cases,rs4969239 was significantly associated with set shifting times,with G allele carriers used longer time than others and had a worse set shifting function(B=-17.55,F=7.13,P=0.008),and rs9901648 was significantly associated with color interference time,with AA genotype carriers used longer time than others and had a worse inhibition function(B=1.82,F=8.84,P=0.003).In further analysis,the association between rs9901648 and color interference only existed in male participants with ADHD(F=11.33,P=0.001).Conclusions BAIAP2 gene possibly contributes to the set shifting and inhibition impairment in children with ADH

关 键 词：注意力缺陷障碍伴多动 脑特异性血管发生抑制剂1相关蛋白2基因 执行功能 关联研究 

分 类 号：R749.94[医药卫生—神经病学与精神病学]