title: Polymorphism in SNAP29 gene promoter region associated with schizophrenia.
abstract: Linkage studies indicate that chromosome 22q contains a locus, or loci, for schizophrenia (SZ) and bipolar disorder (BPD). Furthermore, the congenital disorder velo cardio facial syndrome (VCFS), which is usually caused by a 22q11 microdeletion, is associated with an increased prevalence of psychiatric disease, including SZ and BPD. One plausible candidate gene that maps to 22q11, in a region deleted in the most common form of VCFS, is SNAP29, a member of the SNAP-25 family of SNARE proteins. To search for possible functional mutations in SNAP29 that could be analyzed as candidates for 22q11-linked psychiatric problems, exons, intron-exon junctions and the promoter region were screened. No coding variants were found, although a silent mutation at codon 6 and three single nucleotide polymorphisms (SNPs) were identified in the 5' untranslated and promoter regions. One SNP, an A-->G transition 923 [corrected] nucleotides upstream of the transcription start site, showed a moderately significant difference in the distribution of alleles and genotypes in patients with SZ compared with controls (allele frequency: chi(2) = 5.57, 1 df, P = 0.018; genotype: chi(2) = 9.49, 2 df, P = 0.009; odds ratio = 1.59, 95% Cl = 1.08--2.34). No significant difference was found in patients with BPD. Although the functional significance of this mutation is not known, the tetranucleotide core sequence of the ets and IK2 families of transcription factors is altered as a result of the SNP. These data suggest that a mutation in the SNAP29 gene promoter region, or a mutation in linkage disequilibrium with the promoter SNP, may be involved in the pathogenesis of chromosome 22-linked SZ.
authors.affiliation: Department of Psychiatry, Division of Psychiatry Research, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, New York 10461, USA.
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: F
authors.initials: F
authors.lastname: Guan
authors.forename: D F
authors.initials: DF
authors.lastname: Papolos
authors.forename: N
authors.initials: N
authors.lastname: Rajouria
authors.forename: C S
authors.initials: CS
authors.lastname: Fann
authors.forename: H M
authors.initials: HM
authors.lastname: Lachman
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics; D002892:Chromosomes, Human, Pair 22; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D013572:Synaptic Vesicles / Q000502:physiology; D050825:Synaptosomal-Associated Protein 25
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25