title: CYP1A2 polymorphisms in slow melatonin metabolisers: a possible relationship with autism spectrum disorder?
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: W
authors: W
authors: Braam
authors: H
authors: H
authors: Keijzer
authors: H
authors: H
authors: Struijker Boudier
authors: R
authors: R
authors: Didden
authors: M
authors: M
authors: Smits
authors: L
authors: L
authors: Curfs
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000235:genetics / Q000378:metabolism; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000378:metabolism; D002675:Child, Preschool; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D010865:Pilot Projects; D011110:Polymorphism, Genetic; D012463:Saliva / Q000378:metabolism; D007319:Sleep Initiation and Maintenance Disorders / Q000235:genetics* / Q000378:metabolism
chemical_list: C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D008550:Melatonin