Huang Yi, Liu Xiehe, Li Tao, Guo Lanting, Ma Xiaohong, Yuan Guanggu, Peng Rong
Institute of Mental Health, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041 P. R. China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2002 Apr;19(2):100-3.
To investigate whether DRD4 exon III48 bp variant number tandem repeat(VNTR) polymorphism is associated with tic disorder.
One hundred and twenty-two nucleus families were collected using Structured clinical interview for genetic study of Tourette syndrome and related disorders for family-based association analysis of tic disorder and DRD4 exon III 48bp VNTR polymorphism. One hundred and twenty-two trios were divided into two groups: tic disorder group (82 trios of Tourette syndrome or chronic tic disorder, TS&CT) and tic disorder accompanied with attention deficit and hyperactivity disorder (ADHD) group (40 trios of Tourette syndrome or chronic tic disorder accompanied with ADHD, TS&ADHD). Transmission disequilibrium test (TDT), in addition to polymerase chain reaction and VNTR technique were conducted in 122 trios.
There exist 5 alleles at this polymorphic locus in this sample including DRD4 exon III 48bp 2-6 repeats. No transmission disequilibrium was found between DRD4 exon III 48 bp VNTR and tic disorder (chi square=7.44, P 0.12); however, when the sample was divided into two groups, transmission disequilibrium was noticed between the cases of TS&ADHD and this locus by overall allele-wise analysis (chi square=11.74, P 0.02), and there exists transmission disequilibrium exclusively between 5 or 6 repeats of 48bp VNTR(longer alleles) by allele-wise analysis (chi square=10.57, P 0.032, chi square=6.13, P 0.01). No transmission disequilibrium was seen between TS&CT and DRD4 exon III 48bp VNTR(chi square=3.38, P 0.50).
The results of this study have revealed an association between the longer alleles of DRD4 exon III 48bp VNTR polymorphism and tic disorder accompanied with ADHD, thus suggesting a possible genetic risk factor of tic disorder accompanied with ADHD in Chinese.
探讨多巴胺D4受体(DRD4)基因第三外显子48bp可变数目串联重复序列(VNTR)多态性与抽动障碍是否相关。
采用针对抽动秽语综合征及相关障碍的结构化临床访谈收集122个核心家庭,用于抽动障碍与DRD4基因第三外显子48bp VNTR多态性的家系关联分析。122个三联体被分为两组:抽动障碍组(82个抽动秽语综合征或慢性抽动障碍三联体,TS&CT)和伴有注意缺陷多动障碍(ADHD)的抽动障碍组(40个伴有ADHD的抽动秽语综合征或慢性抽动障碍三联体,TS&ADHD)。对122个三联体进行传递不平衡检验(TDT),同时采用聚合酶链反应和VNTR技术。
该样本中此多态性位点存在5个等位基因,包括DRD4基因第三外显子48bp的2 - 6次重复。未发现DRD4基因第三外显子48bp VNTR与抽动障碍之间存在传递不平衡(卡方 = 7.44,P > 0.12);然而,当样本分为两组时,通过总体等位基因分析发现TS&ADHD病例与该位点之间存在传递不平衡(卡方 = 11.74,P < 0.02),并且通过等位基因分析发现仅在48bp VNTR的5或6次重复(较长等位基因)之间存在传递不平衡(卡方 = 10.57,P < 0.032,卡方 = 6.13,P < 0.01)。未发现TS&CT与DRD4基因第三外显子48bp VNTR之间存在传递不平衡(卡方 = 3.38,P > 0.50)。
本研究结果揭示了DRD4基因第三外显子48bp VNTR多态性的较长等位基因与伴有ADHD的抽动障碍之间存在关联,从而提示在中国伴有ADHD的抽动障碍可能存在遗传风险因素。