Association study between genetic variants at the VAMP2 and VAMP3 loci and bipolar affective disorder.
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.
Abou Jamra
Rami
R
Institute of Human Genetics, University of Bonn, Bonn, Germany. rami.aboujamra@uni-bonn.de
Gobina
Carl Motinda
CM
Becker
Tim
T
Georgi
Alexander
A
Schulze
Thomas G
TG
Schmael
Christine
C
Cichon
Sven
S
Propping
Peter
P
Rietschel
Marcella
M
Nöthen
Markus M
MM
Schumacher
Johannes
J
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*
C494807:VAMP2 protein, human; C494946:VAMP3 protein, human; D050988:Vesicle-Associated Membrane Protein 2; D051040:Vesicle-Associated Membrane Protein 3