title: Hyperserotonemia in autism: the potential role of 5HT-related gene variants.
abstract: Increased platelet serotonin level (PSL) has been consistently found in a portion of autistic patients. Suggested mechanisms for hyperserotonemia in autism have been increased synthesis of serotonin (5HT) by tryptophan hydroxylase (TPH), increased uptake into platelets through 5HT transporter (5HTt), diminished release from platelets through 5HT2A receptor (5HT2Ar) and decreased metabolism by monoamine oxydase (MAOA). The allelic influence of genes, encoding the mentioned 5HT elements, on PSL was investigated in 63 autistic subjects. Our study shows that 5HTt-LPR and -1438AG 5HT(2Ar) genotypes did not significantly affect PSL. However, significantly higher PSLs were observed in subjects with "cc" genotype of a218c TPH and subjects with "4" genotype of uVNTR MAOA. In addition, when TPH-cc and MAOA-4 were combined as "high 5HT" genotypes, a correlative increase in PSL was observed with the increase in the number of "high 5HT" genotypes. These results suggest a possible synergistic effect of genes regulating 5HT synthesis/degradation in dysregulation of the peripheral 5HT homeostasis of autistic patients.
authors.affiliation: Department of Animal Physiology, Faculty of Science, University of Zagreb, Zagreb, Croatia. dubravka@zg.biol.pmf.hr
authors.forename: Dubravka
authors.initials: D
authors.lastname: Hranilović
authors.forename: Ruder
authors.initials: R
authors.lastname: Novak
authors.forename: Marina
authors.initials: M
authors.lastname: Babić
authors.forename: Mislav
authors.initials: M
authors.lastname: Novokmet
authors.forename: Zorana
authors.initials: Z
authors.lastname: Bujas-Petković
authors.forename: Branimir
authors.initials: B
authors.lastname: Jernej
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000097:blood* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics / Q000502:physiology; D011110:Polymorphism, Genetic; D044348:Receptors, Serotonin, 5-HT2 / Q000235:genetics*; D012701:Serotonin / Q000096:biosynthesis / Q000097:blood* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000502:physiology
chemical_list: D044348:Receptors, Serotonin, 5-HT2; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D008995:Monoamine Oxidase