Rgs 2 gene polymorphisms as modulators of anxiety in humans?
Article First Online: 01 June 2006 Received: 09 September 2005 Accepted: 15 February 2006 Summary.
Rgs2 (regulator of G-protein signalling 2) gene recently was reported as a quantitative trait gene for anxious behaviour in mice and male Rgs2 knockout mice have been shown to be more anxious than wildtype mice. Therefore we investigated four non-coding single nucleotide polymorphisms in a sample of 173 patients with panic disorder and 173 matched controls of German descent. At the genotype level all four SNPs were associated with panic disorder (
p = 0.02–0.05). At the haplotype level the strongest association was observed for a haplotype containing SNP3 and SNP 4 (subgroup men and men with agoraphobia: p = 0.01 and 0.03). This points towards a functional polymorphism at the 3′ end of the gene. Our results support the hypothesis that variations of the Rgs2 gene play a role also for the development of anxiety in humans. Keywords: Rgs2, chromosom 1q31, panic disorder, linkage disequilibrium, polymorphisms, case-control-study References Crowe, RR, Goedken, R, Samuelson, S, Wilson, R, Nelson, J, Noyes, R 2001 Genomewide survey of panic disorder Am J Med Genet 105 105 109 PubMed CrossRef Google Scholar Flint, J 2003 Analysis of quantitative trait loci that influence animal behaviour J Neurobiol 54 46 77 PubMed CrossRef Google Scholar Gelernter, J, Bonvicini, K, Page, G, Woods, SW, Goddard, AW, Kruger, S, Pauls, DL, Goodson, S 2001 Linkage genome scan for loci predisposing to panic disorder or agoraphobia Am J Med Genet 105 548 557 PubMed CrossRef Google Scholar Goodwin, RD, Faravelli, C, Rosi, S, Cosci, F, Truglia, E, de Graaf, R, Wittchen, HU 2005 The epidemiology of panic disorder and agoraphobia in Europe Eur Neuropsychopharmacol 15 435 443 PubMed CrossRef Google Scholar Hettema, JM, Neale, MC, Kendler, KS 2001 A review and meta-analysis of the genetic epidemiology of anxiety disorders Am J Psychiatry 158 1568 1578 PubMed CrossRef Google Scholar Hoehn-Saric, R, McLeod, DR, Zimmerli, WD 1991 Psychophysiological response patterns in panic disorder Acta Psychiatr Scand 83 4 11 PubMed Google Scholar Huang, LJ, Durick, K, Weiner, JA, Chun, J, Taylor, SS 1997 D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain Proc Natl Acad Sci USA 94 11184 11189 PubMed CrossRef Google Scholar Mannuzza, 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 PubMed CrossRef Google Scholar Michael, B, Spitzer, RL, Gibbon, M, Williams, JBW 1996Structured Clinical Interview for DSM-IV Axis I Disorders, Clinical Version (SCID-CV) American Psychiatric Press, Inc Washington, D.C. Google Scholar Oliviera-dos-Santos, AJ, Matsumoto, G, Snow, BE, Bai, D, Houston, FP, Whishaw, IQ, Mariathasan, S, Sasaki, T, Wakeham, A, Ohashi, PS, Roder, JC, Barnes, CA, Siderovski, DP, Penninger, JM 2000 Regulation of T cell activation, anxiety, and male aggression by RGS2 Proc Natl Acad Sci USA 97 12272 12277 CrossRef Google Scholar Robins, LN, Wing, J, Wittchen, HU, Helzer, JE, Babor, TF, Burke, J, Farmer, A, Jablenski, A, Pickens, R, Regier, DA, Sartorius, N, Towle, LH 1988 The composite international diagnostic interview. An epidemiologic instrument suitable for use in conjunction with different diagnostic systems and in different cultures Arch Gen Psychiatry 45 1069 1077 PubMed Google Scholar Smoller, JW, Acierno, JS, Rosenbaum, JF, Biederman, J, Pollack, MH, Meminger, S, Pava, JA, Chadwick, LA, White, C, 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 PubMed CrossRef Google Scholar Vieland, VJ, Goodman, DW, Chapman, T, Fyer, AJ 1996 New segregation analysis of panic disorder Am J Med Genet 67 147 153 PubMed CrossRef Google Scholar Watson, N, Linder, ME, Druey, KM, Kehrl, JH, Blumer, KJ 1996 RGS family members: GTPase activating proteins for heterotrimeric G-protein alpha-subunits Nature 383 172 175 PubMed CrossRef Google Scholar Weissmann, MM, Bland, RC, Canino, GJ, Faravelli, C, Greenwald, S, Hwu, HG, Joyce, PR, Karam, EG, Lee, CK, Lellouch, J, Lepine, JP, Newman, SC, Oakley-Browne, MA, Rubio-Stipec, M, Wells, JE, Wickramaratne, PJ, Wittchen, HU, Yeh, EK 1997 The cross-national epidemiology of panic disorder Arch Gen Psychiatry 54 305 309 Google Scholar Wittchen, HU, Garczynski, E, Pfister, H 1997Composite International Diagnostic Interview according to ICD-10 and DSM-IV Hogrefe Göttingen Google Scholar Yalcin, B, Willis-Owen, SAG, Fullerton, J, Meesaq, A, Deacon, RM, Rawlins, JNP, Copley, RR, Morris, AP, Flint, J, Mott, R 2004 Genetic dissection of a behavioral quantitative trait locus shows that Rgs2 modulates anxiety in mice Nat Genet 36 1197 11202 PubMed CrossRef Google Scholar Zhao, JH, Sham, PC 2002 Faster haplotype frequency estimation using unrelated subjects Hum Hered 53 53 56 CrossRef Google Scholar