title: Mutation scanning of the androgen receptor gene in patients with psychiatric disorders reveals highly conserved variants in alcoholic and phobia patients.
abstract: Sex steroids exert potent effects on mood and mental state in humans. They may contribute to the risk of psychiatric disorders. To investigate this hypothesis, coding and splice junction sequences of the androgen receptor gene were scanned in genomic DNA samples to search for variants affecting protein structure and expression (VAPSEs). Ninety-six schizophrenics, along with pilot samples of patients with bipolar disorder, attention-deficit hyperactivity disorder, alcoholism and autism were analyzed with DOVAM-S, a robotically enhanced, optimized form of single-strand conformation polymorphism analysis. A total of 669 kb of genomic sequence was analyzed. Two VAPSEs were identified: R726L was found in one of 17 scanned alcoholics, and P516S, a novel VAPSE, was identified in one of three phobia patients. There were no length trends of the CAG triplets associated with schizophrenia. R726L and P516S occur at highly conserved amino acids. Further study is required to assess whether these VAPSEs contribute to the risk of alcoholism or phobia or other diseases.
authors.affiliation: Department of Molecular Genetics, City of Hope National Medical Center, Duarte, California 91010-3000, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Yan
authors.forename: Jinong
authors.initials: J
authors.lastname: Feng
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Ian R
authors.initials: IR
authors.lastname: Jones
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Heston
authors.forename: Steve S
authors.initials: SS
authors.lastname: Sommer
mesh_terms: D000437:Alcoholism / Q000235:genetics; D019943:Amino Acid Substitution; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D014644:Genetic Variation; D006801:Humans; D001523:Mental Disorders / Q000235:genetics*; D020125:Mutation, Missense; D010698:Phobic Disorders / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011944:Receptors, Androgen / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics; D016037:Single-Blind Method; D018911:Trinucleotide Repeats
chemical_list: C410798:AR protein, human; D003062:Codon; D011944:Receptors, Androgen