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Published in: Journal of Neural Transmission 9/2008

01-09-2008 | Biological Psychiatry - Original Article

Association between polymorphisms in the vesicle-associated membrane protein-associated protein A (VAPA) gene on chromosome 18p and bipolar disorder

Authors: Falk W. Lohoff, Andrew E. Weller, Paul J. Bloch, Aleksandra H. Nall, Thomas N. Ferraro, Wade H. Berrettini

Published in: Journal of Neural Transmission | Issue 9/2008

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Abstract

Linkage studies in bipolar disorder (BPD) suggest that a susceptibility locus exists on chromosome 18p11. The vesicle-associated membrane protein-associated protein A (VAPA) gene maps to this region. VAPA interacts with presynaptic proteins and is necessary for vesicular neurotransmission. Dysregulation of synaptic neurotransmission might contribute to the pathophysiology of BPD. In this study, we hypothesize that genetic variations in the VAPA gene contribute to BPD. We tested this hypothesis by genotyping 6 SNPs (rs494015; rs29193; rs29162; rs29145; rs29067; rs29066) in BPD patients (n = 570) and healthy controls (n = 730). Genotype and allele frequencies were compared between groups using Chi square contingency analysis. Linkage disequilibrium (LD) between markers was calculated and estimated haplotype frequencies were compared between groups. Single marker analysis revealed an association of rs29067 and rs29066 with BPD; however, after permutation correction, only rs29066 showed a trend towards an allelic association (P = 0.066). Haplotype analysis did not show any significant association with disease after permutation correction. Our results provide suggestive evidence of an association between SNPs in the 3′UTR of the VAPA gene and BPD. Interestingly, these SNPs are in close proximity to the microsatellite marker D18S464, which showed significant signals in previous linkage studies of BPD. Additional studies are necessary to confirm and elucidate the role of VAPA as a susceptibility gene for BPD on chromosome 18p.
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Metadata
Title
Association between polymorphisms in the vesicle-associated membrane protein-associated protein A (VAPA) gene on chromosome 18p and bipolar disorder
Authors
Falk W. Lohoff
Andrew E. Weller
Paul J. Bloch
Aleksandra H. Nall
Thomas N. Ferraro
Wade H. Berrettini
Publication date
01-09-2008
Publisher
Springer Vienna
Published in
Journal of Neural Transmission / Issue 9/2008
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI
https://doi.org/10.1007/s00702-008-0093-9

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