Department Advisium, 's Heeren Loo Zuid-Veluwe, Wekerom, The Netherlands Department of Clinical Chemistry, Rijnstate Hospital, Arnhem, The Netherlands Department of Pharmacology and Toxicology, Maastricht University, Maastricht, The Netherlands Special Education, Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands Department of Neurology, Gelderse Vallei Hospital, Ede, The Netherlands Department of Clinical Genetics, University Maastricht/Academic Hospital, Maastricht, The Netherlands.
J Intellect Disabil Res. 2013 Nov;57(11):993-1000. doi: 10.1111/j.1365-2788.2012.01595.x. Epub 2012 Jul 23.
In some of our patients with intellectual disabilities (ID) and sleep problems, the initial good response to melatonin disappeared within a few weeks after starting treatment. In these patients melatonin levels at noon were extremely high (>50 pg/ml). We hypothesise that the disappearing effectiveness is associated with slow metabolisation of melatonin because of a single nucleotide polymorphism (SNP) of CYP1A2.
In this pilot study we analysed DNA extracted from saliva samples of 15 consecutive patients with disappearing effectiveness of melatonin. Saliva was collected at noon and 4 pm for measuring melatonin levels.
In all patients' salivary melatonin levels at noon were >50 or melatonin half time was > 5 h. A SNP was found in eight of 15 patients. The allele 1C was found in two patients and in six patients the 1F allele was found.
Of 15 patients with disappearing effectiveness of melatonin, seven were diagnosed with autism spectrum disorder, and in four of them a SNP was found. The other eight patients were known with a genetic syndrome. In six of them behaviour was considered to be autistic-type and in three of them a SNP was found. This finding may give a new direction for research into the genetic background of autism.
在一些有智力障碍（ID）和睡眠问题的患者中，开始治疗后几周内，最初对褪黑素的良好反应消失了。这些患者中午的褪黑素水平极高（>50pg/ml）。我们假设，褪黑素的有效性消失与褪黑素代谢缓慢有关，因为 CYP1A2 的单核苷酸多态性（SNP）。
在这项初步研究中，我们分析了 15 名褪黑素疗效消失的连续患者的唾液样本中的 DNA。中午和下午 4 点采集唾液以测量褪黑素水平。
所有患者中午的唾液褪黑素水平均>50pg/ml 或褪黑素半衰期>5 小时。在 15 名患者中的 8 名中发现了一个 SNP。在两名患者中发现了等位基因 1C，在六名患者中发现了 1F 等位基因。
在褪黑素疗效消失的 15 名患者中，有 7 名被诊断为自闭症谱系障碍，其中 4 名患者发现了 SNP。其他 8 名患者患有已知的遗传综合征。在其中 6 名患者中，行为被认为是自闭症型，其中 3 名患者发现了 SNP。这一发现可能为自闭症的遗传背景研究提供了新的方向。
