title: Association between polymorphisms in the vesicle-associated membrane protein-associated protein A (VAPA) gene on chromosome 18p and bipolar disorder.
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.
authors.affiliation: Department of Psychiatry, Translational Research Laboratories, University of Pennsylvania School of Medicine, Center for Neurobiology and Behavior, 125 South 31st Street, Room 2213, Philadelphia, PA 19104, USA. lohoff@mail.med.upenn.edu
authors.forename: Falk W
authors.initials: FW
authors.lastname: Lohoff
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Weller
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Bloch
authors.forename: Aleksandra H
authors.initials: AH
authors.lastname: Nall
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Ferraro
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000235:genetics*; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D005819:Genetic Markers; C114051:VAPA protein, human; D033921:Vesicular Transport Proteins