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          Institute: MPI für Psychiatrie     Collection: Publikationen MPI für Psychiatrie     Display Documents



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ID: 395624.0, MPI für Psychiatrie / Publikationen MPI für Psychiatrie
Combined Effects of Exonic Polymorphisms in CRHR1 and AVPR1B Genes in a Case/Control Study for Panic Disorder
Authors:Keck, M. E.; Kern, N.; Erhardt, A.; Unschuld, P. G.; Ising, M.; Salyakina, D.; Müller, M. B.; Knorr, C. C.; Lieb, R.; Hohoff, C.; Krakowitzky, P.; Maier, W.; Bandelow, B.; Fritze, J.; Deckert, J.; Holsboer, F.; Müller-Myhsok, B.; Binder, E. B.
Language:English
Date of Publication (YYYY-MM-DD):2008-10-05
Title of Journal:American Journal of Medical Genetics Part B-Neuropsychiatric Genetics
Journal Abbrev.:Am. J. Med. Genet. B
Volume:147B
Issue / Number:7
Start Page:1196
End Page:1204
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Accumulating evidence from animal studies suggests that the corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) neuropeptide systems, contribute to anxiety behavior. To investigate whether polymorphisms in the genes regulating these two systems may alter susceptibility to anxiety disorders in humans, we genotyped 71 single nucleotide polymorphisms (SNPs) in CRH, CRHR1, CRHR2, AVP, AVPR1A, AVPR1B in a German sample from Munich with patients suffering from panic disorder and matched healthy controls (n = 186/n = 299). Significant associations were then replicated in a second German sample with 173 patients with panic disorder and 495 controls. In both samples separately and the combined sample, SNPs within CHRH1 and AVPR1B were nominally associated with panic disorder. We then tested two locus multiplicative and interaction effects of polymorphisms of these two genes on panic disorder. Fifteen SNP pairs showed significant multiplicative effects in both samples. The SNP pair with the most significant association in the combined sample (P = 0.00057), which withstood correction for multiple testing, was rs878886 in CRHR1 and rs28632197 in AVPR1B. Both SNPs are of potential functional relevance as rs878886 is located in the 3' untranslated region of the CRHR1 and rs28632197 leads to an arginine to histidine amino acid exchange at position 364 of AVPR1B which is located in the intracellular C-terminal domain of the receptor. These data suggest that polymorphisms in the AVPR1B and the CRHR1 genes alter the susceptibility to panic disorder. (C) 2008 Wiley-Liss, Inc.
Free Keywords:anxiety disorders; association; SNP; CRHR1; AVPR1B
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:N. N.
Affiliations:MPI für Psychiatrie
External Affiliations:[Keck, Martin E.; Kern, Nikola; Erhardt, Angelika; Unschuld, Paul G.; Ising, Marcus; Salyakina, Daria; Mueller, Marianne B.; Knorr, Carolin C.; Lieb, Roselind; Holsboer, Florian; Mueller-Myhsok, Bertram; Binder, Elisabeth B.] Max Planck Inst Psychiat, D-80804 Munich, Germany.; [Keck, Martin E.] Neurosci Ctr Zurich ZNZ, Oetwil Am See Zurich, Switzerland.; [Hohoff, Christa] Univ Munster, Dept Psychiat, Munster, Germany.; [Krakowitzky, Petra] Univ Munster, Inst Transfus Med, Munster, Germany.; [Maier, Wolfgang] Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany.; [Bandelow, Borwin] Univ Gottingen, Dept Psychiat, Gottingen, Germany.; [Fritze, Juergen] Univ Frankfurt, Dept Psychiat, Frankfurt, Germany.; [Deckert, Juergen] Univ Wurzburg, Dept Psychiat, D-8700 Wurzburg, Germany.
Identifiers:ISI:000259979500026 [ID No:1]
ISSN:1552-4841 [ID No:2]
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