Park L, Nigg J T, Waldman I D, Nummy K A, Huang-Pollock C, Rappley M, Friderici K H
Genetics Program, Michigan State University, East Lansing, MI 48824, USA.
Mol Psychiatry. 2005 Jun;10(6):572-80. doi: 10.1038/sj.mp.4001605.
Attention-deficit hyperactivity disorder (ADHD) is a heritable disorder, prevalent from childhood through adulthood. Although the noradrenergic (NA) system is thought to mediate a portion of the pathophysiology of ADHD, genes in this pathway have not been investigated as frequently as those in the dopaminergic system. Previous association studies of one candidate gene in the NA system, ADRA2A, showed inconsistent results with regard to an MspI polymorphism. In the current study, two nearby single-nucleotide polymorphisms, which define HhaI and DraI restriction fragment length polymorphisms, were also genotyped and were in significant linkage disequilibrium with the MspI RFLP. Transmission disequilibrium tests (TDTs) in a sample of 177 nuclear families showed significant association and linkage of the DraI polymorphism with the ADHD combined subtype (P=0.03), and the quantitative TDT showed association of this polymorphism with the inattentive (P=0.003) and hyperactive-impulsive (P=0.015) symptom dimensions. The haplotype that contained the less common allele of the DraI polymorphism likewise showed a strong relationship with the inattentive (P=0.001) and hyperactive-impulsive (P=0.004) symptom dimensions. This study supports the hypothesis that an allele of the ADRA2A gene is associated and linked with the ADHD combined subtype and suggests that the DraI polymorphism of ADRA2A is linked to a causative polymorphism.
注意缺陷多动障碍（ADHD）是一种遗传性疾病，从儿童期到成年期都有发生。尽管去甲肾上腺素能（NA）系统被认为介导了ADHD病理生理学的一部分，但该途径中的基因尚未像多巴胺能系统中的基因那样被频繁研究。先前对NA系统中一个候选基因ADRA2A的关联研究，在MspI多态性方面显示出不一致的结果。在当前研究中，还对定义HhaI和DraI限制性片段长度多态性的两个相邻单核苷酸多态性进行了基因分型，并且它们与MspI限制性片段长度多态性存在显著的连锁不平衡。在177个核心家庭样本中的传递不平衡检验（TDT）显示，DraI多态性与ADHD合并亚型存在显著关联和连锁（P = 0.03），定量TDT显示该多态性与注意力不集中（P = 0.003）和多动冲动（P = 0.015）症状维度存在关联。包含DraI多态性较不常见等位基因的单倍型同样与注意力不集中（P = 0.001）和多动冲动（P = 0.004）症状维度显示出强烈关联。这项研究支持了ADRA2A基因的一个等位基因与ADHD合并亚型相关联并连锁的假设，并表明ADRA2A的DraI多态性与一个致病多态性连锁。
