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注意缺损多动障碍(attention defic it hyperactivity d isorder,ADHD)是儿童期多见行为障碍。男孩发病多于女孩。家系、双生儿和寄养子研究显示该障碍发生具有遗传基础。但是病因尚不清楚。分子遗传学和药理学研究表明ADHD涉及到多巴胺和去甲肾上腺素等神经递质系统,一系列报告发现ADHD与多巴胺D4受体(DRD4)、多巴胺转运体(DAT1)和儿茶酚-O-甲基转移酶(COMT)等基因相关联。以往研究表明ADHD与X染色体上DXS7位点和MAOA基因相关联,而DXS7是紧密连锁于MAO基因。依此假设,应用基因组扫描技术探讨ADHD在X染色体上易感位点。采用TDT方法分析X染色体上48个DNA标志的多态性与中国人群中84个ADHD核心家系间的连锁关系,ADHD诊断依据DSM-Ⅲ-R标准。TDT分析结果观察到如下位点与ADHD相连锁,DXS1214(TDT:χ2=18.1,df=7,P<0.01),DXS8102(TDT:χ2=7.9,df=3,P<0.05),DXS1068(TDT:χ2=21.9,df=9,P<0.01),DXS8015(TDT:χ2=14.6,df=7,P<0.05),DXS1059(TDT:χ2=27.8,df=10,P<0.01)和DXS8088(TDT:χ2=20.4,df=3,P<0.01)。研究资料提示X染色体上Xp11.4-p21和Xq23区域可能存在ADHD的易感基因。
Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioral disorder. Boys have more disease than girls. Family, twins, and foster child studies have shown that this disorder has a genetic basis. But the cause is not clear. Molecular genetic and pharmacological studies have shown that ADHD involves neurotransmitter systems such as dopamine and norepinephrine. A series of reports found that ADHD is associated with dopamine D4 receptor (DRD4), dopamine transporter (DAT1) and catechol-O- Methyltransferase (COMT) and other genes associated. Previous studies have shown that ADHD is associated with the DXS7 locus on the X chromosome and the MAOA gene, whereas DXS7 is tightly linked to the MAO gene. Based on this hypothesis, genome-wide scan technique was used to investigate ADHD susceptibility loci on the X chromosome. The TDT method was used to analyze the linkage relationship between the 48 DNA markers on chromosome X and the 84 pedigrees of ADHD in Chinese population. The diagnosis of ADHD was based on the DSM-III-R standard. The results of TDT showed that the following sites were linked to ADHD: DXS1214 (TDT: χ2 = 18.1, df = 7, P <0.01) (DXT = χ2 = 14.6, df = 7, P <0.05), DXS8059 (TDT: χ2 = 27.8, df = 10, P <0.01) and DXS8088 TDT: χ2 = 20.4, df = 3, P <0.01). Research data suggest that the X chromosome Xp11.4-p21 and Xq23 region may exist ADHD susceptibility genes.