A polymorphism at the 3′-untranslated region of the CLOCK gene is associated with adult attention-deficit hyperactivity disorder
A polymorphism at the 3′-untranslated region of the CLOCK gene is associated with adult attention-deficit hyperactivity disorder
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DOI：
10.1002/ajmg.b.30602
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发表时间：
2008-04-05
影响因子：
2.8
通讯作者：
Thome, Johannes
中科院分区：
文献类型：
--
作者：
Kissling, Christian;Retz, Wolfgang;Thome, Johannes
注意力缺陷多动障碍(ADHD)经常出现在儿童时期，大约50%的病例会持续到成年。一些研究表明，ADHD、昼夜节律和未服用药物的ADHD患者的睡眠障碍之间存在关系。由于ADHD是一种非常复杂的疾病，具有高遗传负荷，涉及多个中等效应的基因，我们假设成人ADHD与参与昼夜计时系统的基因之间存在联系。昼夜节律运动输出周期蛋白kaput(CLOCK)基因rs1801260的3‘-UTR多态与睡眠模式紊乱有关，尽管C等位基因和更具争议的T等位基因都被认为是不同晚上偏好程度的危险因素。这项研究比较了143名患有和不患有ADHD的受试者和他们的rs1801260基因携带者的ADHD精神病理学自评和访谈测量，以检验ADHD与时钟多态的一个等位基因相关联的假设。T>；C单核苷酸多态性rs1801260在从血液样本中提取的DNA中进行了基因分型。采用非参数单因素方差分析和后组配对比较，比较各基因型与ADHD评分之间的相关性。在每个成人多动症评估和rs1801260基因多态之间都有很强的，显著的关联(P<；0.001)，至少有一个T突变是危险等位基因。这是第一项表明生物钟机制中的基因多态是成人ADHD的直接或相关因素的研究。(C)2007年Wiley-Liss，Inc.
Attention-deficit hyperactivity disorder (ADHD) is frequently found in childhood and persists in about 50% of cases into adulthood. Several studies demonstrate a relationship between ADHD, circadian rhythmicity and sleeping disturbances in unmedicated ADHD patients. Since ADHD is a very complex disease with a high genetic load involving multiple genes of moderate effect, we hypothesized a link between adult ADHD and genes involved in the circadian timekeeping system. A 3'-UTR polymorphism of the circadian locomotor output cycles protein kaput (CLOCK) gene, rs1801260, has been linked to disturbed sleep patterns, although both the C-allele and more controversially the T-allele have been proposed as risk factors for different measures of evening preference. This study compared self-rating and interview based measures of ADHD psychopathology of 143 subjects with and without ADHD with their rs1801260 genotype to test the hypothesis that ADHD is linked to one of the alleles of the CLOCK polymorphism. The T > C single nucleotide polymorphism rs1801260 was genotyped in DNA isolated from blood samples. The associations between genotype and ADHD-scores were compared using non-parametric ANCOVA with post hoc pairwise comparisons. There was a strong, significant association (P < 0.001) between each of the adult ADHD assessments and the rs1801260 polymorphism with at least one T-mutation being the risk allele. This is the first study suggesting that a polymorphism of a gene within the circadian "clock" mechanism is a direct or linked contributing factor in adult ADHD. (C) 2007 Wiley-Liss, Inc.