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  • Original Research Article
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Polymorphism in SNAP29 gene promoter region associated with schizophrenia

Molecular Psychiatry volume 6, pages 193–201 (2001)Cite this article

A Corrigendum to this article was published on 29 August 2001

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 849 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: χ2 = 5.57, 1 df, P = 0.018; genotype: χ2 = 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.

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Acknowledgements

The authors want to thank Drs Rael Strous, Margaret Woemer, Gianni Feadda, Sabine Veit, Jan Volavka and Karen Nolan for blood samples from schizophrenia subjects. Some DNA samples were obtained from the Coriell Institute in conjunction with The National Institutes of Mental Health Bipolar Genetics Initiative, a multi-site study performed by four independent research teams in collaboration with extramural staff from the National Institute of Mental Health (NIMH). The four Principal Investigators and Co-Investigators from the four sites are: Indiana University, Indianapolis, IN, U01 MH46282, John Numberger, MD, PhD, Marvin Miller, MD, and Elizabeth Bowman, MD; Washington University, St Louis, MO, U01 MH46280, Theodore Reich, MD, Allison Goate, PhD, and John Rice, PhD; Johns Hopkins University, Baltimore MD, U01 MH46274, J Raymond DePaulo, Jr, MD, Sylvia Simpson, MD, MPH, and Colin Stine, PhD: NIMH Intramural Research Program, Clinical Neurogenetics Branch, Bethesda, MD, Elliot Gershon, MD, Diane Kazuba, BA, and Elizabeth Maxwell.

TS is supported by the American Psychiatric Association, Program for Minority Research Training in Psychiatry, and by a Young Investigator Award from NARSAD. HML is a recipient of a NARSAD Independent Investigator Award. DFP is a recipient of a NARSAD Independent Investigator Award.

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  1. Department of Psychiatry, Division of Psychiatry Research, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, 10461, New York, USA

    T Saito, F Guan, D F Papolos, N Rajouria, C S J Fann & H M Lachman

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Saito, T., Guan, F., Papolos, D. et al. Polymorphism in SNAP29 gene promoter region associated with schizophrenia. Mol Psychiatry 6, 193–201 (2001). https://doi.org/10.1038/sj.mp.4000825

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