Turic D, Williams H, Langley K, Owen M, Thapar A, O'Donovan M C
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom.
Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):64-7. doi: 10.1002/ajmg.b.30123.
Neurobiological studies have suggested that altered dopaminergic function may contribute to the etiology of attention deficit hyperactivity disorder (ADHD). The gene encoding catechol-O-methyltransferase (COMT) is an attractive candidate for ADHD susceptibility as it plays a major role in the degradation of dopamine. Moreover, a functional Val158Met polymorphism in COMT that alters the activity of the encoded protein has been strongly implicated in frontal lobe function, with the high activity Valine allele being associated with poorer performance, and ADHD is thought to involve fronto-striatal pathways. We have examined this functional variant for association with ADHD in a family based association sample comprising 279 probands and their parents. We have also examined two other markers in the COMT gene (rs737865, rs165599) which, together with the Val/Met variant, have recently been shown to be associated with altered COMT expression rather than enzyme activity. No evidence for association was observed with any single marker or haplotype in a sample of 279 affected children and their parents.
神经生物学研究表明，多巴胺能功能改变可能与注意力缺陷多动障碍（ADHD）的病因有关。编码儿茶酚-O-甲基转移酶（COMT）的基因是ADHD易感性的一个有吸引力的候选基因，因为它在多巴胺降解中起主要作用。此外，COMT基因中的一个功能性Val158Met多态性改变了编码蛋白的活性，这与额叶功能密切相关，高活性的缬氨酸等位基因与较差的表现相关，而ADHD被认为涉及额叶-纹状体通路。我们在一个由279名先证者及其父母组成的基于家系的关联样本中，研究了这个功能性变体与ADHD的关联。我们还研究了COMT基因中的另外两个标记（rs737865，rs165599），最近发现它们与COMT表达改变而非酶活性相关，并且与Val/Met变体一起研究。在279名受影响儿童及其父母的样本中，未观察到任何单个标记或单倍型与ADHD相关的证据。
