title: Association of promoter variants in the alpha7 nicotinic acetylcholine receptor subunit gene with an inhibitory deficit found in schizophrenia.
abstract: BACKGROUND
  The alpha7 neuronal nicotinic acetylcholine receptor subunit gene (CHRNA7) has been implicated as a candidate gene for schizophrenia, and for an auditory sensory processing deficit found in the disease, by both genetic linkage at 15q14 and biochemical data. The expression of CHRNA7 is reduced in several brain regions in schizophrenic subjects compared with control subjects. This study presents DNA sequence analysis of the core promoter region for CHRNA7 in schizophrenic and control subjects.
  
  
  METHODS
  Single-strand conformation polymorphism analysis and DNA sequencing were used for mutation screening of the core promoter in the CHRNA7 gene. The sample included subjects from 166 schizophrenic families and 165 controls. Controls had no evidence of current or past psychosis and had auditory evoked potentials recorded.
  
  
  RESULTS
  Multiple polymorphic patterns were identified in the CHRNA7 core promoter in both schizophrenic and control subjects. Functional analysis of polymorphisms indicated that transcription was reduced. The prevalence of functional promoter variants was statistically greater in schizophrenic subjects than in the controls. Presence of an alpha7 promoter polymorphism in controls was associated with failure to inhibit the P50 auditory evoked potential response.
  
  
  CONCLUSIONS
  Although linkage disequilibrium with other genetic alterations cannot be excluded, the CHRNA7 core promoter variants, found in this study, may contribute to a common pathophysiologic feature of schizophrenia.
authors.affiliation: Department of Psychiatry, Campus Box C-268-71, University of Colorado Health Sciences Center, 4200 E Ninth Ave, Denver, CO 80262, USA. Sherry.Leonard@UCHSC.edu
authors.forename: Sherry
authors.initials: S
authors.lastname: Leonard
authors.forename: Judith
authors.initials: J
authors.lastname: Gault
authors.forename: Jan
authors.initials: J
authors.lastname: Hopkins
authors.forename: Judith
authors.initials: J
authors.lastname: Logel
authors.forename: Ruby
authors.initials: R
authors.lastname: Vianzon
authors.forename: Margaret
authors.initials: M
authors.lastname: Short
authors.forename: Carla
authors.initials: C
authors.lastname: Drebing
authors.forename: Ralph
authors.initials: R
authors.lastname: Berger
authors.forename: Diana
authors.initials: D
authors.lastname: Venn
authors.forename: Pinkhas
authors.initials: P
authors.lastname: Sirota
authors.forename: Gary
authors.initials: G
authors.lastname: Zerbe
authors.forename: Ann
authors.initials: A
authors.lastname: Olincy
authors.forename: Randal G
authors.initials: RG
authors.lastname: Ross
authors.forename: Lawrence E
authors.initials: LE
authors.lastname: Adler
authors.forename: Robert
authors.initials: R
authors.lastname: Freedman
mesh_terms: D001308:Auditory Perceptual Disorders / Q000235:genetics / Q000473:pathology / Q000523:psychology; D001921:Brain / Q000473:pathology; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D004252:DNA Mutational Analysis; D005072:Evoked Potentials, Auditory / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D009433:Neural Inhibition / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D012565:Schizophrenic Psychology; D017422:Sequence Analysis, DNA; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor