title: Association study between genetic variants at the VAMP2 and VAMP3 loci and bipolar affective disorder.
abstract: OBJECTIVE
  Vesicle-associated membrane proteins 2 and 3 (VAMP2 and VAMP3) are required for the release of D-serine, a competitive agonist of the neurotransmitter glycine at the glutamatergic N-methyl-D-aspartate receptors. Several lines of evidence point to an involvement of altered D-serine levels in the central nervous system in the aetiology of bipolar affective disorder (BPAD). Strong association findings between BPAD and two genes, G72 and DAAO, which are involved in the enzymatic degradation of D-serine, are reported. Based on the functional evidence and on the hypothesis that further genes, which are involved in the regulation of D-serine, could be involved in the disease aetiology, we considered VAMP2 and VAMP3 as candidate genes for BPAD.
  
  
  METHODS
  We analyzed three and four single nucleotide polymorphism (SNP) markers covering VAMP2 and VAMP3, respectively, in an initial BPAD case-control sample of German descent (409 cases, 407 controls). For replication, we analyzed three SNP markers covering VAMP2 in a second sample of the same ethnicity (378 cases, 384 controls).
  
  
  RESULTS
  Although no association was found for VAMP3 markers, we observed evidence of association with SNPs at the VAMP2 locus in the initial sample (P values between 0.005 and 0.033). To validate these findings, we analyzed a second BPAD sample and failed to replicate the initial findings at the single-marker and haplotypic level.
  
  
  CONCLUSIONS
  In conclusion, our results do not suggest that a common genetic variant at VAMP2 or VAMP3 contributes to the development of BPAD in German patients.
authors.affiliation: Institute of Human Genetics, University of Bonn, Bonn, Germany. rami.aboujamra@uni-bonn.de
authors.forename: Rami
authors.initials: R
authors.lastname: Abou Jamra
authors.forename: Carl Motinda
authors.initials: CM
authors.lastname: Gobina
authors.forename: Tim
authors.initials: T
authors.lastname: Becker
authors.forename: Alexander
authors.initials: A
authors.lastname: Georgi
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Christine
authors.initials: C
authors.lastname: Schmael
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Peter
authors.initials: P
authors.lastname: Propping
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Johannes
authors.initials: J
authors.lastname: Schumacher
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050988:Vesicle-Associated Membrane Protein 2 / Q000235:genetics*; D051040:Vesicle-Associated Membrane Protein 3 / Q000235:genetics*
chemical_list: C494807:VAMP2 protein, human; C494946:VAMP3 protein, human; D050988:Vesicle-Associated Membrane Protein 2; D051040:Vesicle-Associated Membrane Protein 3