title: Genetic variation in melatonin pathway enzymes in children with autism spectrum disorder and comorbid sleep onset delay.
abstract: Sleep disruption is common in individuals with autism spectrum disorder (ASD). Genes whose products regulate endogenous melatonin modify sleep patterns and have been implicated in ASD. Genetic factors likely contribute to comorbid expression of sleep disorders in ASD. We studied a clinically unique ASD subgroup, consisting solely of children with comorbid expression of sleep onset delay. We evaluated variation in two melatonin pathway genes, acetylserotonin O-methyltransferase (ASMT) and cytochrome P450 1A2 (CYP1A2). We observed higher frequencies than currently reported (p < 0.04) for variants evidenced to decrease ASMT expression and related to decreased CYP1A2 enzyme activity (p ≤ 0.0007). We detected a relationship between genotypes in ASMT and CYP1A2 (r(2) = 0.63). Our results indicate that expression of sleep onset delay relates to melatonin pathway genes.
authors: Sleep Disorders Division, Department of Neurology, Vanderbilt University Medical Center, 1161 21st Ave. S., Nashville, TN, 37232, USA, olivia.j.veatch@vanderbilt.edu.
authors: Olivia J
authors: OJ
authors: Veatch
authors: Julie S
authors: JS
authors: Pendergast
authors: Melissa J
authors: MJ
authors: Allen
authors: Roberta M
authors: RM
authors: Leu
authors: Carl Hirschie
authors: CH
authors: Johnson
authors: Sarah H
authors: SH
authors: Elsea
authors: Beth A
authors: BA
authors: Malow
mesh_terms: D000121:Acetylserotonin O-Methyltransferase / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000150:complications* / Q000201:enzymology / Q000235:genetics*; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D004252:DNA Mutational Analysis; D058068:Endophenotypes; D005838:Genotype; D006801:Humans; D008297:Male; D008550:Melatonin / Q000096:biosynthesis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications* / Q000201:enzymology / Q000235:genetics*
chemical_list: C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D000121:Acetylserotonin O-Methyltransferase; D008550:Melatonin