多巴胺D_4受体基因多态性与注意缺陷多动障碍的关联分析

Association of dopamine D_4 gene polymorphism with attention deficit hyperactivity disorder in children

目的 探讨注意缺陷多动障碍 (ADHD)与多巴胺D4 受体 (DRD4)基因第 3外显子 48bp可变数目顺向重复 (VNTR)多态性的关系。方法 对 176例ADHD患儿 (病例组 )、98个ADHD核心家系 (家系组 ,共 2 94人 )及 119名正常对照 (对照组 )进行ADHD与DRD4基因 48bpVNTR多态性的关联分析。结果 所测人群中的 48bpVNTR多态性表现为 2～ 6次重复 (分别为 40 7bp、45 5bp、5 0 3bp、5 5 1bp及 5 99bp) ;其中以 4次重复 (73 9% )和 2次重复 (2 1 8% )最为常见 ;尚未发现 7次重复序列。病例组 2 / 2基因型 (6 3% )显著低于对照组 (14 3 % ;P =0 0 2 ) ,这种差异主要表现在ADHD混合型。对 98个家系的精确多等位基因不平衡传递检验 ,未发现等位基因与ADHD存在连锁不平衡 (χ2 =5 119,ν=4,P >0 0 5 )。结论 DRD4基因 48bpVNTR多态性主要集中于 4次重复序列片段上 ;48bp片段的重复次数可能与ADHD相关 ,重复

Objective To investigate association of the 48 bp variable number of tandem repeat (VNTR) polymorphism in the dopamine D 4 receptor gene (DRD4) exon Ⅲ with attention deficit hyperactivity disorder (ADHD) in Chinese children Methods A case control association study and a family based association study with Exact Transmission Disequilibrium Test (ETDT) were used to analyze the association of polymorphism in the dopamine D 4 receptor gene exon Ⅲ with ADHD 176 ADHD children diagnosed according to DSM IV criteria, 119 normal controls and 98 parental/affected trios were recruited in the study According to structured clinical diagnostic interview scale, the ADHD children were classified into three subtypes Then the association of 48 bp VNTR polymorphism with each ADHD subtype was analyzed Results In this sample, the repeat numbers of 48 bp were 2 to 6, the common alleles were n =4 (73 9%) and n =2 (21 8%), and the allele n =7 repeat was not found in this sample The DRD4*2/DRD4*2 genotype was less common in ADHD subjects than in normal controls( P =0 02), especially in ADHD combined subtype Conclusions The n =4 and n =2 types account for most of the alleles of DRD4 48 bp repeat polymorphism in Chinese population The repeat number of 48 bp may be associated with ADHD, and the n =2 allele may reduce the susceptibility to ADHD in Chinese children