【摘要】 目的:探讨单纯注意缺陷多动障碍与去甲肾上腺素转运体基因(NET1)多态之间的关联。方法:依据美国精神障碍诊断与统计手册第4版(DSM-IV)诊断标准,采用儿童临床诊断性会谈量表(CDIS)进行共患病评定以及亚型划分,该量表将ADHD分为3个亚型:注意缺陷为主型(ADHD-I)、多动冲动为主型(ADHD-HI)和混合型(ADHD-C)。纳入936名健康对照和491例单纯ADHD儿童(含350个核心家系),其中有276例ADHD-I儿童,34例ADHD-HI儿童,181例ADHD-C儿童。进行NET1基因的6个单核苷酸多态性(SNPs)位点的基因型检测,采用传递不平衡检验、χ2检验对单个SNP位点及单体型与单纯ADHD进行关联分析。结果:家系研究结果显示,在女性单纯ADHD家系中,rs36009的C等位基因存在过度传递趋势(24 vs.10,P=0.016,校正P=0.090),由rs36009、rs2242447构成的TC单体型存在传递减少的趋势(13 vs.25,P=0.044,校正P=0.071)。分亚型分析显示,rs2279805的T等位基因在单纯ADHD-I家系以及男性单纯ADHD-I家系中存在过度传递趋势(86 vs.57,P=0.015,校正P=0.091)或者过度传递(71 vs.40,P=0.003,校正P=0.018)。在女性单纯ADHD-I家系中,rs36009的C等位基因存在过度传递(21 vs.7,P=0.008,校正P=0.039),rs36009、rs2242447构成的TC单体型存在传递减少的趋势(9 vs.21,P=0.029,校正P=0.058)。病例对照关联分析结果显示,rs3785143的C等位基因在单纯ADHD样本中的分布频率具有高于对照组的趋势(0.870 vs.0.832,P=0.010,校正P=0.056),在ADHD-I以及男性单纯ADHD-I样本中的分布频率高于对照组(0.882 vs.0.832,校正P=0.025)或者具有高于对照组的趋势(0.894 vs.0.842,P=0.010,校正P=0.054)。结论:NET1可能是单纯ADHD,尤其是单纯ADHD-I的易感基因。更多还原

【Abstract】 Objective:To investigate the association between NET1 and attention-deficit/hyperactivity disorder( ADHD only). Methods: Based on The Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition( DSM-IV) diagnosis criteria,Clinical Diagnostic Interview Scale( CDIS) w as used to assesses comorbidities and the three DSM-IV subtypes: ADHD inattentive type( ADHD-I),ADHD hyperactive-impulsive type( ADHD-HI), and ADHD combined type( ADHD-C). Totally 936 normal controls and 491 children w ith ADHD only( including 350 trios) w ere enrolled,including 276 children w ith ADHD-I only,34 w ith ADHD-HI only,181 w ith ADHD-C only. Six single nucleotide polymorphisms( SNPs) of NET1 w ere genotyped. Family-based association and casecontrol studies w ere conducted to investigate the association of each SNP and / or haplotypes w ith children w ith ADHD only using transmission disequilibrium test( TDT) and chi-square test. Results: For family-based analyses, the C allele of rs36009 had a tendency to be over-transmitted( 24 vs. 10,nominal P = 0. 016,empirical P = 0. 090) and the TC haplotype consisted of rs36009-rs2242447 had a tendency to be under-transmitted( 13 vs. 25,nominal P = 0. 044,empirical P = 0. 071) in female trios w ith ADHD only. For different subtypes,the T allele of rs22279805 had a tendency to be over-transmitted or w as over-transmitted in trios w ith ADHD-I only( 86 vs. 57,nominal P = 0. 015,empirical P = 0. 091) and male trios w ith ADHD-I only( 71 vs. 40, nominal P = 0. 003, empirical P = 0. 018). The C allele of rs36009 w as over-transmitted( 21 vs. 7,nominal P = 0. 008,empirical P = 0. 039) and the TC haplotype consisted of rs36009-rs2242447 had a tendency to be under-transmitted( 9 vs. 21,nominal P = 0. 029, empirical P = 0. 058) in female trios w ith ADHD-I only. For case-control studies,the C allele of rs3785143 show ed higher frequency in children w ith ADHD only than normal controls( 0. 870 vs. 0. 832,nominal P = 0. 010,empirical P = 0. 056). For different subtypes,the C allele of rs3785143 show ed higher frequency in children w ith ADHD-I only( 0. 882 vs. 0. 832,empirical P = 0. 025) and male children w ith ADHD-I only( 0. 894 vs. 0. 842,nominal P = 0. 010,empirical P = 0. 054) than normal controls. Conclusion: It suggests that NET1 w as probably among the susceptibility genes of children w ith ADHD only,especially of children w ith ADHD-I only.更多还原