Association study between genetic variants at the VAMP2 and VAMP3 loci and bipolar affective disorder

Rami Abou Jamra, Carl Motinda Gobina, Tim Becker, Alexander Georgi, Thomas G. Schulze, Christine Schmael, Sven Cichon, Peter Propping, Marcella Rietschel, Markus M. Nöthen, Johannes Schumacher

Research output: Contribution to journalArticle

Abstract

OBJECTIVES: 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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)199-203
Number of pages5
JournalPsychiatric Genetics
Volume18
Issue number4
DOIs
StatePublished - Aug 2008
Externally publishedYes

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Vesicle-Associated Membrane Protein 3
Vesicle-Associated Membrane Protein 2
Genetic Association Studies
Mood Disorders
Bipolar Disorder
Serine
Single Nucleotide Polymorphism
Genes
N-Methyl-D-Aspartate Receptors
Glycine
Neurotransmitter Agents
Central Nervous System

Keywords

  • 17q
  • 1p
  • Case-control
  • D-serine
  • German
  • SNARE

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Genetics
  • Biological Psychiatry
  • Neuroscience(all)

Cite this

Jamra, R. A., Gobina, C. M., Becker, T., Georgi, A., Schulze, T. G., Schmael, C., ... Schumacher, J. (2008). Association study between genetic variants at the VAMP2 and VAMP3 loci and bipolar affective disorder. Psychiatric Genetics, 18(4), 199-203. https://doi.org/10.1097/YPG.0b013e3283050a83

Association study between genetic variants at the VAMP2 and VAMP3 loci and bipolar affective disorder. / Jamra, Rami Abou; Gobina, Carl Motinda; Becker, Tim; Georgi, Alexander; Schulze, Thomas G.; Schmael, Christine; Cichon, Sven; Propping, Peter; Rietschel, Marcella; Nöthen, Markus M.; Schumacher, Johannes.

In: Psychiatric Genetics, Vol. 18, No. 4, 08.2008, p. 199-203.

Research output: Contribution to journalArticle

Jamra, RA, Gobina, CM, Becker, T, Georgi, A, Schulze, TG, Schmael, C, Cichon, S, Propping, P, Rietschel, M, Nöthen, MM & Schumacher, J 2008, 'Association study between genetic variants at the VAMP2 and VAMP3 loci and bipolar affective disorder', Psychiatric Genetics, vol. 18, no. 4, pp. 199-203. https://doi.org/10.1097/YPG.0b013e3283050a83
Jamra, Rami Abou ; Gobina, Carl Motinda ; Becker, Tim ; Georgi, Alexander ; Schulze, Thomas G. ; Schmael, Christine ; Cichon, Sven ; Propping, Peter ; Rietschel, Marcella ; Nöthen, Markus M. ; Schumacher, Johannes. / Association study between genetic variants at the VAMP2 and VAMP3 loci and bipolar affective disorder. In: Psychiatric Genetics. 2008 ; Vol. 18, No. 4. pp. 199-203.
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abstract = "OBJECTIVES: 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. CONCLUSION: 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.",
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AU - Jamra, Rami Abou

AU - Gobina, Carl Motinda

AU - Becker, Tim

AU - Georgi, Alexander

AU - Schulze, Thomas G.

AU - Schmael, Christine

AU - Cichon, Sven

AU - Propping, Peter

AU - Rietschel, Marcella

AU - Nöthen, Markus M.

AU - Schumacher, Johannes

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N2 - OBJECTIVES: 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. CONCLUSION: 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.

AB - OBJECTIVES: 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. CONCLUSION: 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.

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