脑源性神经营养因子基因单核苷酸多态与注意缺陷多动障碍的关系  

Association between Single Nucleotide Polymorphisms of Brain-Derived Neurotrophic Factor Gene and Attention Deficit Hyperactivity Disorder

作　　者：李海梅[1] 钱秋谨[1] 王玉凤[1] 杨莉[1] 陈芸[1] 吉宁[1] 刘璐[1] 李泽华[1] 

机构地区：[1]北京大学精神卫生研究所儿童研究室,卫生部精神卫生学重点实验室,北京100191

出　　处：《实用儿科临床杂志》2011年第4期277-282,共6页Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金(81071109,30770774);卫生行业科研专项经费项目(200802073);“十一·五”国家科技支撑计划项目(2007BAI17B03)

摘　　要：目的探讨脑源性神经营养因子(BDNF)基因单核苷酸多态性(SNP)位点rs6265、rs7103411和rs11030104多态与注意缺陷多动障碍(ADHD)及其亚型之间的关系。方法根据美国《精神障碍诊断与统计手册》第4版(DSM-Ⅳ)中ADHD诊断标准,共收集1 842例散发ADHD病例及其组成的1 271个ADHD家系和957例健康对照者分别进行家系和病例对照研究。在美国生物系统公司生产的7900 HT型荧光定量PCR仪提供的技术平台上完成等位基因分型试验,采用遗传分析统计软件Haploview 4.2进行传递不平衡检验(TDT)、2χ检验和单体型分析对ADHD及其表型进行关联分析,并对P值进行置换检验的校正。结果 BDNF基因的SNP位点rs6265/C、rs11030104/A、rs7103411/T以及CAT单体型在女性单纯ADHD家系中过度传递,在女性单纯ADHD患者中频率明显高于健康对照组(Pa<0.05)。BDNF基因rs6265/T和TT基因型、rs11030104/G及GG基因型、rs7103411/C及TT基因型和TGC单体型在男性单纯ADHD混合型(ADHD-C)家系中有过度传递趋势,在男性ADHD-C亚型患儿中频率有高于健康对照组的趋势。结论 BDNF基因单核苷酸多态性变异可能与ADHD的病理机制有关,可能是作用于较精细的同质性较高的ADHD亚组,且这种作用机制存在性别差异。Objective To explore the association between rs6265,rs7103411 and rs11030104 of single nucleotide polymorphism（SNP） of the brain-derived neurotrophic factor（BDNF） gene and attention deficit hyperactivity disorder（ADHD） and the subtypes of ADHD.Methods Transmission disequilibrium test（TDT） and case-control association studies were conducted within a sample of 1 271 nuclear ADHD families,1 842 ADHD cases,and 957 healthy controls.Diagnosis and ADHD subtypes were ascertained according to Diagnostic and Statistical Manual of Mental Disorders 4th Edition（DSM-Ⅳ） criteria using American Clinical Diagnostic Interviewing Scales.The SNP was genotyped through 7900 HT real-time polymerase chain reaction genotyping technique.TDT,chi-square test,and haplotype analysis were employed for statistical analysis with the genetic analysis statistics software Haploview 4.2,and permutaion test was used to evaluate gene-wide statistical significance furthermore.Results The rs6265/C,rs11030104/A,rs7103411/T allele and CAT haplotype were preferentially transmitted to pure ADHD girls.The case-control study revealed that they were more frequent in pure ADHD girls than those in healthy control group（P0.05）.The rs6265/T and TT,rs11030104/G and GG,rs7103411/C and TT allele and TGC haplotype had the tendency to be preferentially transmitted to male ADHD Commix（ADHD-C）.The case-control study revealed that they also had the tendency to be more frequent in male ADHD-C than those in healthy control group.Conclusion SNP of BDNF gene may be related to pathologic mechanisms of ADHD,and this association suggests genetic sexual dimorphism.

关 键 词：注意缺陷多动障碍 脑源性神经营养因子 遗传 性别差异 

分 类 号：R749.94[医药卫生—神经病学与精神病学]