Polymorphism in SNAP29 gene promoter region associated with schizophrenia

Citation
T. Saito et al., Polymorphism in SNAP29 gene promoter region associated with schizophrenia, MOL PSYCHI, 6(2), 2001, pp. 193-201
Citations number
71
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
MOLECULAR PSYCHIATRY
ISSN journal
1359-4184 → ACNP
Volume
6
Issue
2
Year of publication
2001
Pages
193 - 201
Database
ISI
SICI code
1359-4184(200103)6:2<193:PISGPR>2.0.ZU;2-X
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 psychiat ric disease, including SZ and BPD, One plausible candidate gene that maps t o 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 func tional mutations in SNAP29 that could be analyzed as candidates for 22q11-l inked psychiatric problems, exons, intron-exon junctions and the promoter r egion were screened. No coding variants were found, although a silent mutat ion at codon 6 and three single nucleotide polymorphisms (SNPs) were identi fied in the 5' untranslated and promoter regions. One SNP, an A-->G transit ion 849 nucleotides upstream of the transcription start site, showed a mode rately significant difference in the distribution of alleles and genotypes in patients with SZ compared with controls (allele frequency: chi (2) = 5.5 7, 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 kno wn, the tetranucleotide core sequence of the ets and IK2 families of transc ription 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 dis equilibrium with the promoter SNP, may be involved in the pathogenesis of c hromosome 22-linked SZ.