Combined effects of exonic polymorphisms in CRHR1 and AVPR1B genes in a case/control study for panic disorder

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 di...

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Published inAmerican journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 147B; no. 7; pp. 1196 - 1204
Main Authors Keck, Martin E., Kern, Nikola, Erhardt, Angelika, Unschuld, Paul G., Ising, Marcus, Salyakina, Daria, Müller, Marianne B., Knorr, Carolin C., Lieb, Roselind, Hohoff, Christa, Krakowitzky, Petra, Maier, Wolfgang, Bandelow, Borwin, Fritze, Jürgen, Deckert, Jürgen, Holsboer, Florian, Müller-Myhsok, Bertram, Binder, Elisabeth B.
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 05.10.2008
Wiley-Liss
Subjects
3' Untranslated Regions
Adult
Adult and adolescent clinical studies
anxiety disorders
Anxiety disorders. Neuroses
association
AVPR1B
Biological and medical sciences
Case-Control Studies
CRHR1
Exons - genetics
Female
Genetic Predisposition to Disease - genetics
Genotype
Humans
Male
Medical genetics
Medical sciences
Middle Aged
Mutation, Missense
Panic disorder
Panic Disorder - genetics
Polymorphism, Single Nucleotide
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Receptors, Corticotropin-Releasing Hormone - genetics
Receptors, Vasopressin - genetics
SNP
Panic
Association
Gene
AVPR1B
SNP
Anxiety disorder
anxiety disorders
Case control study
Single nucleotide polymorphism
CRHR1
Online AccessGet full text

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Abstract 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. © 2008 Wiley‐Liss, Inc.
AbstractList 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.
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. © 2008 Wiley‐Liss, Inc.
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.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.
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. © 2008 Wiley‐Liss, Inc.
Author Knorr, Carolin C.
Holsboer, Florian
Binder, Elisabeth B.
Salyakina, Daria
Lieb, Roselind
Kern, Nikola
Krakowitzky, Petra
Maier, Wolfgang
Bandelow, Borwin
Müller, Marianne B.
Keck, Martin E.
Ising, Marcus
Fritze, Jürgen
Unschuld, Paul G.
Deckert, Jürgen
Erhardt, Angelika
Müller-Myhsok, Bertram
Hohoff, Christa
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Issue 7
Keywords Panic
Association
Gene
AVPR1B
SNP
Anxiety disorder
anxiety disorders
Case control study
Single nucleotide polymorphism
CRHR1
Language English
License http://onlinelibrary.wiley.com/termsAndConditions#vor
CC BY 4.0
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istex:66E843DB11521E4B2E8A7B2097DA75D01F18C38D
ark:/67375/WNG-CJC5V489-4
M.E. Keck and N. Kern contributed equally to the work.
Please cite this article as follows: Keck ME, Kern N, Erhardt A, Unschuld PG, Ising M, Salyakina D, Müller MB, Knorr CC, Lieb R, Hohoff C, Krakowitzky P, Maier W, Bandelow B, Fritze J, Deckert J, Holsboer F, Müller-Myhsok B, Binder EB. 2008. Combined Effects of Exonic Polymorphisms in CRHR1 and AVPR1B Genes in a Case/Control Study for Panic Disorder. Am J Med Genet Part B 147B:1196-1204.
German Government
National Genome Research Network (NGFN) - No. 01GS0481
ArticleID:AJMG30750
Please cite this article as follows: Keck ME, Kern N, Erhardt A, Unschuld PG, Ising M, Salyakina D, Müller MB, Knorr CC, Lieb R, Hohoff C, Krakowitzky P, Maier W, Bandelow B, Fritze J, Deckert J, Holsboer F, Müller‐Myhsok B, Binder EB. 2008. Combined Effects of Exonic Polymorphisms in CRHR1 and AVPR1B Genes in a Case/Control Study for Panic Disorder. Am J Med Genet Part B 147B:1196–1204.
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PublicationTitle American journal of medical genetics. Part B, Neuropsychiatric genetics
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Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Pütz B, et al. 2004. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant tretament. Nat Genet 36: 1319-1325.
Griebel G, Simiand J, Serradeil-Le Gal C, Wagnon J, Pascal M, Scatton B, et al. 2002. Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR 149415, suggest an innovative approach for the treatment of stress-related disorders. Proc Natl Acad Sci USA 99: 6370-6375.
Jessop DS. 1999. Review: Central non-glucocorticoid inhibitors of the hypothalamo-pituitary-adrenal axis. J Endocrinol 160: 169-180.
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Manuzza S, Fyer AJ, Klein DF, Endicott J. 1986. Schedule for affective disorders and schizophrenia-Lifetime version modified for the study of anxiety disorders (SADS-LA): Rationale and conceptual development. J Psychiatr Res 20: 317-325.
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Tharmalingam S, King N, De Luca V, Rothe C, Koszycki D, Bradwejn J, et al. 2006. Lack of association between the corticotrophin-releasing hormone receptor 2 gene and panic disorder. Psychiatr Genet 16: 93-97.
Hamilton M. 1960. A rating scale for depression. J Neurol Neurosurg Psychiatry 23: 56-62.
Muller MB, Preil J, Renner U, Zimmermann S, Kresse AE, Stalla GK, et al. 2001. Expression of CRHR1 and CRHR2 in mouse pituitary and adrenal gland: Implications for HPA system regulation. Endocrinology 142: 4150-4153.
Smoller JW, Acierno JS, Rosenbaum JF, Biederman J, Bulzacchelli M, Slaugenhaupt SA. 2001. Targeted genome screen of panic disorder and anxiety disorder proneness using homology to murine QTL regions. Am J Med Genet 105: 195-206.
Perlis RH, Mischoulon D, Smoller JW, Wan YJ, Lamon-Fava S, Lin KM, et al. 2003. Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment. Biol Psychiatry 54: 879-883.
Bhattacharya SK, Bhattacharya A, Chakrabarti A. 1998. Anxiogenic activity of intraventricularly administered arginine vasopressin in the rat. Biogenic Amines 14: 367-385.
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Sanchez MM, Young LJ, Plotsky PM, Insel TR. 1999. Autoradiographic and in situ hybridization localization of corticotropin-releasing factor 1 and 2 receptors in nonhuman primate brain. J Comp Neurol 408: 365-377.
Coryell W, Noyes R, Schlechte J. 1989. The significance of HPA axis disturbance in panic disorder. Biol Psychiatry 25: 989-1002.
Domschke K, Hohoff C, Jacob C, Maier W, Fritze J, Bandelow B, et al. 2007. Chromosome 4q31-34panic disorder risk locus: Association of neuropeptide Y Y5 receptor variants. Am J Med Genet B Neuropsychiatr Genet.
Finn DA, Rutledge-Gorman MT, Crabbe JC. 2003. Genetic animal models of anxiety. Neurogenetics 4: 109-135.
Deckert J, Nothen MM, Franke P, Delmo C, Fritze J, Knapp M, et al. 1998. Systematic mutation screening and association study of the A(1) and A(2a) adenosine receptor genes in panic disorder suggest a contribution of the A(2a) gene to the development of disease. Mol Psychiatry 3: 81-85.
Uhr M, Steckler T, Yassouridis A, Holsboer F. 2000. Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. Neuropsychopharmacology 22: 380-387.
Sen S, Villafuerte S, Nesse R, Stoltenberg SF, Hopcian J, Gleiberman L, et al. 2004. Serotonin transporter and GABAA alpha 6 receptor variants are associated with neuroticism. Biol Psychiatry 55: 244-249.
Keck ME, Wigger A, Welt T, Muller MB, Gesing A, Reul JM, et al. 2002. Vasopressin mediates the response of the combined dexamethasone/CRH test in hyper-anxious rats: Implications for pathogenesis of affective disorders. Neuropsychopharmacology 26: 94-105.
Zobel AW, Nickel T, Kunzel HE, Ackl N, Sonntag A, Ising M, Holsboer F. 2000. Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: The first 20 patients treated. J Psychiatr Res 34: 171-181.
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Hamilton SP, Slager SL, Helleby L, Heiman GA, Klein DF, Hodge SE, et al. 2001. No association or linkage between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B receptor and
2006; 31
2001; 142
1990; 15
2002; 51
2002; 99
2004; 68
2004; 24
2004; 9
2005; 21
1999; 82
1998; 43
2005; 29
2003; 54
1999; 408
2001; 105
2004; 36
2003; 6
2004; 34
2003; 2
2003; 4
1988; 45
1959; 32
1996a; 153
1998; 55
1998; 14
2002; 36
1996b; 53
2003; 976
1995; 59
2006; 11
2006; 16
2000; 22
2002; 160q
1996; 93
2002; 2
1997
2007
1999; 20
1998; 138
1999; 8
1989; 25
2001; 25
1996; 10
1983; 36
1999
1995; 7
1993; 14
2004; 55
2002; 26
2007; 316
2006; 84
2001; 6
1986; 20
1960; 23
2004; 16
2000; 34
1999; 160
1994; 14
1998; 3
2003; 28
2007; 86
2003; 64
2001; 158
1994; 51
1998; 33
2005; 57
2005; 14
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– reference: Griebel G, Simiand J, Serradeil-Le Gal C, Wagnon J, Pascal M, Scatton B, et al. 2002. Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR 149415, suggest an innovative approach for the treatment of stress-related disorders. Proc Natl Acad Sci USA 99: 6370-6375.
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– reference: Spina M, Merlo-Pich E, Akwa Y, Baducci C, Basso AM, Zorrilla EP, et al. 2002. Time-dependent induction of anxiogenic-like effects after central infusion of urocortin or corticotropin-releasing factor in the rat. Psychopharmacology 160q: 113-121.
– reference: Deckert J, Nothen MM, Franke P, Delmo C, Fritze J, Knapp M, et al. 1998. Systematic mutation screening and association study of the A(1) and A(2a) adenosine receptor genes in panic disorder suggest a contribution of the A(2a) gene to the development of disease. Mol Psychiatry 3: 81-85.
– reference: Cheng R, Juo SH, Loth JE, Nee J, Iossifov I, Blumenthal R, et al. 2006. Genome-wide linkage scan in a large bipolar disorder sample from the National Institute of Mental Health genetics initiative suggests putative loci for bipolar disorder, psychosis, suicide, and panic disorder. Mol Psychiatry 11: 252-260.
– reference: Sen S, Villafuerte S, Nesse R, Stoltenberg SF, Hopcian J, Gleiberman L, et al. 2004. Serotonin transporter and GABAA alpha 6 receptor variants are associated with neuroticism. Biol Psychiatry 55: 244-249.
– reference: Montkowski A, Barden N, Wotjak C, Stec I, Ganster J, Meaney M, et al. 1995. Long-term antidepressant treatment reduces behavioural deficits in transgenic mice with impaired glucocorticoid receptor function. J Neuroendocrinol 7: 841-845.
– reference: Dunn AJ, Berridge CW. 1990. Physiological and behavioral responses to corticotropin-releasing factor administration: Is CRF a mediator of anxiety or stress responses? Brain Res Rev 15: 71-100.
– reference: Zobel AW, Nickel T, Kunzel HE, Ackl N, Sonntag A, Ising M, Holsboer F. 2000. Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: The first 20 patients treated. J Psychiatr Res 34: 171-181.
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Snippet Accumulating evidence from animal studies suggests that the corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) neuropeptide systems,...
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SubjectTerms 3' Untranslated Regions
Adult
Adult and adolescent clinical studies
anxiety disorders
Anxiety disorders. Neuroses
association
AVPR1B
Biological and medical sciences
Case-Control Studies
CRHR1
Exons - genetics
Female
Genetic Predisposition to Disease - genetics
Genotype
Humans
Male
Medical genetics
Medical sciences
Middle Aged
Mutation, Missense
Panic disorder
Panic Disorder - genetics
Polymorphism, Single Nucleotide
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Receptors, Corticotropin-Releasing Hormone - genetics
Receptors, Vasopressin - genetics
SNP
Title Combined effects of exonic polymorphisms in CRHR1 and AVPR1B genes in a case/control study for panic disorder
URI https://api.istex.fr/ark:/67375/WNG-CJC5V489-4/fulltext.pdf
https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fajmg.b.30750
https://www.ncbi.nlm.nih.gov/pubmed/18384079
https://www.proquest.com/docview/20624459
https://www.proquest.com/docview/69586883
Volume 147B
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