多巴胺转运体蛋白基因G352A多态性与注意缺陷多动障碍的关联分析

Association studies of G352A polymorphism of dopamine transporter gene in Han Chinese attention deficit hyperactivity disorder patients

目的：探讨中国汉族人群中注意缺陷多动障碍(attention deficit hyperactivity disorder，ADHD)与多巴胺转运体蛋白基因(DAT1)第15外显子 G352A 多态性的关系。方法：应用彩色荧光标记序列分析方法寻找突变位点，检测337个 ADHD 患儿，201个 ADHD 核心家系和207个对照 DAT1的新基因位点 G352A 的多态性，并进行传递不平衡检验(transmission disequilibrium test，TDT)和病例对照的关联分析。结果：所测对照人群中 DAT1的 G352A 的等位基因频率，352G 是79.5%，352A 是20.5%。家系和病例对照研究表明，DAT1第15外显子 G352A 基因和ADHD 之间不存在关联。但是按照性别分组后，TDT 结果表明，G352A 基因和 ADHD 女孩可能存在关联，即352G等位基因在 ADHD 女孩中有优先传递的趋势。结论：DAT1第15外显子上的新基因位点 G352A 和 ADHD 之间不存在关联。352G 等位基因在 ADHD 女孩中有优先传递的趋势，但尚需要扩大样本进一步验证才能得出确切结论。

Objective:To investigate association of the new polymorphism G352A in the dopaminetransporter gene(DAT1)exon 15 with attention deficit hyperactivity disorder(ADHD)in Han Chinesechildren.Methods:The new mutant polymorphism G352A in the dopamine transporter gene(DAT1)ex-on 15 was found by the fluorescently-labeled dye-terminators assay.The study samples were comprised of337 ADHD children,207 unrelated controls and 201 integrated ADHD trios(included proband and bio-logical parents).Associations of polymorphisms with ADHD and its subtypes were examined by:(i)comparing cases and controls;and(ii)using family-based association study in transmission-disequilibri-um test(TDT).Results:The allele frequencies at the DAT1 G352A locus in the control samples were79.5% for 352G and 20.5% for 352A respectively.Association studies revealed no association betweenG352A in exon 15 of DAT1 and ADHD.But after a stratification by gender,there was possible associationbetween G352A and ADHD girls:the 352G allele had a tendency to be preferentially transmitted toADHD girls.Conclusion:There is no association between G352A,the new polymorphism,in exon 15 ofDAT1 and ADHD.The 352G allele has a tendency to be preferentially transmitted to ADHD girls,but thefindings require replication before drawing a definitive conclusion.