Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders

• Published in: Journal of pineal research Vol. 51; no. 4; pp. 394 - 399
• Main Authors: Chaste, Pauline, Clement, Nathalie, Botros, Hany Goubran, Guillaume, Jean-Luc, Konyukh, Marina, Pagan, Cécile, Scheid, Isabelle, Nygren, Gudrun, Anckarsäter, Henrik, Rastam, Maria, Ståhlberg, Ola, Gillberg, I. Carina, Melke, Jonas, Delorme, Richard, Leblond, Claire, Toro, Roberto, Huguet, Guillaume, Fauchereau, Fabien, Durand, Christelle, Boudarene, Lydia, Serrano, Emilie, Lemière, Nathalie, Launay, Jean Marie, Leboyer, Marion, Jockers, Ralf, Gillberg, Christopher, Bourgeron, Thomas
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2011
• Subjects: AA-NAT; Acetylserotonin O-Methyltransferase; Acetylserotonin O-Methyltransferase - genetics; ADHD; Arylalkylamine N-Acetyltransferase; Arylalkylamine N-Acetyltransferase - genetics; ASMT; Attention Deficit Disorder with Hyperactivity; Attention Deficit Disorder with Hyperactivity - genetics; but little is known about the genetic variability of this pathway in humans. Here; but no significant enrichment compared with the general population. Among these variations; Clinical Medicine; Female; G-Protein-Coupled; genes; Genetic Variation; Genetic Variation - genetics; Genetics; Genetics Receptors; Humans; Klinisk medicin; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Melatonin; Melatonin - genetics; Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of melatonin signaling has been reported in a broad range of diseases; MT1; MTNR1A; MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with Attention Deficit/Hyperactivity Disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD; Nerve Tissue; Nerve Tissue Proteins - genetics; Proteins; Psychiatry; Psykiatri; Receptor; Receptor, Melatonin, MT1 - genetics; receptors; Receptors, G-Protein-Coupled - genetics; we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) — detected exclusively in patients with ADHD — for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD; we sequenced all the genes of the melatonin pathway - AA-NAT
• ISSN: 0742-3098; 1600-079X; 1600-079X
• DOI: 10.1111/j.1600-079X.2011.00902.x

:  Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway –AA‐NAT, ASMT, MTNR1A, MTNR1B and GPR50 – in 321 individuals from Sweden including 101 patients with attention‐deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) – detected exclusively in patients with ADHD – for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.