Das Manali, Mukhopadhyay Kanchan
Manovikas Biomedical Research and Diagnostic Centre, E.M. Bypass, Kolkata, India.
Am J Med Genet B Neuropsychiatr Genet. 2007 Sep 5;144B(6):826-9. doi: 10.1002/ajmg.b.30513.
Genetic alterations in the dopaminergic system are frequently observed in association with attention deficit hyperactivity disorder (ADHD) and a 40 bp variable number of tandem repeats (VNTR) in the 3'-untranslated region (3'-UTR) of the dopamine transporter gene (DAT1) has been investigated in different populations. Both significant association and lack of association with the10 repeat allele (10R) of DAT1 VNTR have been reported. Objective of the present investigation was to examine association of this polymorphism with ADHD in Indian children. Genotypic data obtained from ADHD probands (n = 79), their parents (n = 148) and control individuals (n = 153) were analyzed for haplotype-based haplotype relative risk analysis (HHRR), transmission disequilibrium test (TDT), and family-based association test (FBAT). HHRR analysis revealed significant (P = 0.009) transmission of shorter alleles (< or =9R). TDT analysis of informative ADHD families (n = 32) also exhibited highly significant transmission of the shorter alleles (P = 0.002). Further analysis by FBAT showed preferential transmission (P = 0.019) of the 9R allele from parents to ADHD probands. It can be inferred from the data obtained that the DAT1 3'-UTR 9R allele may confer risk of ADHD in the Indian population.
多巴胺能系统的基因改变常与注意力缺陷多动障碍（ADHD）相关，多巴胺转运体基因（DAT1）3'非翻译区（3'-UTR）中一个40bp的可变串联重复序列（VNTR）已在不同人群中进行了研究。关于DAT1 VNTR的10重复等位基因（10R），既有显著关联的报道，也有缺乏关联的报道。本研究的目的是检验这种多态性与印度儿童ADHD的关联。对从ADHD先证者（n = 79）、其父母（n = 148）和对照个体（n = 153）获得的基因型数据进行基于单倍型的单倍型相对风险分析（HHRR）、传递不平衡检验（TDT）和基于家系的关联检验（FBAT）。HHRR分析显示较短等位基因（≤9R）有显著（P = 0.009）传递。对信息充分的ADHD家系（n = 32）进行的TDT分析也显示较短等位基因有高度显著的传递（P = 0.002）。通过FBAT进一步分析显示9R等位基因从父母向ADHD先证者有优先传递（P = 0.019）。从所获得的数据可以推断，DAT1 3'-UTR 9R等位基因可能使印度人群有患ADHD的风险。
