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Variation in the gene of the nuclear transcription factor \u201ccAMP\u2010responsive element modulator\u201d (CREM) might contribute to its pathogenesis. CREM knock\u2010out mice exhibit significantly less anxiety behavior than wild\u2010type mice and the alternative <jats:italic>CREM<\/jats:italic> gene product \u201cinducible cAMP early repressor\u201d (ICER) plays a pivotal role in the hypothalamo\u2010pituitary\u2010adrenal (HPA) axis, which is disturbed in panic disorder. We characterized the genomic organization of the human <jats:italic>CREM<\/jats:italic> gene and performed a systematic mutation screening by means of single stranded conformational analysis (SSCA) in a sample of 40 German patients with panic disorder (DSM\u2010III\u2010R). Four novel single nucleotide polymorphisms in CREM promoters P 1 and P 4, one trinucleotide (ATT)\u2010repeat polymorphism in CREM promoter P 2\u2014generating the ICER isoform\u2014and a rare amino acid substitution in CREM exon glut 2 were identified. Association analysis in an extended sample of German patients (n\u2009=\u200988) revealed a significant excess of the shorter CREM P 2 promoter eight\u2010repeat trinucleotide allele and of genotypes containing the eight\u2010repeat trinucleotide allele in panic disorder (<jats:italic>P<\/jats:italic>\u2009=\u20090.02), in particular in panic disorder without agoraphobia (<jats:italic>P<\/jats:italic>\u2009=\u20090.001). A replication study in independent Italian (n\u2009=\u200976) and Spanish (n\u2009=\u200962) samples, however, failed to confirm this observation. This suggests that the CREM P 2 promoter trinucleotide polymorphism is not a major susceptibility factor in the pathogenesis of panic disorder. Functional analysis of the observed CREM P 2 promoter polymorphism as well as studies in independent panic disorder samples are necessary. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.b.10018","type":"journal-article","created":{"date-parts":[[2003,1,29]],"date-time":"2003-01-29T15:36:34Z","timestamp":1043854594000},"page":"70-78","source":"Crossref","is-referenced-by-count":20,"title":["Human nuclear transcription factor gene <i>CREM<\/i>: Genomic organization, mutation screening, and association analysis in panic disorder"],"prefix":"10.1002","volume":"117B","author":[{"given":"K.","family":"Domschke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Kuhlenb\u00e4umer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Schirmacher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Lorenzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Armengol","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"DiBella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Gratacos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.S.","family":"Garritsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.M.","family":"N\u00f6then","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Franke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Sand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Fritze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Perez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Maier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Sibrowski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"X.","family":"Estivill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Bellodi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.B.","family":"Ringelstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Arolt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Martin\u2010Santos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Catalano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"St\u00f6gbauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Deckert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1996.01830040059010"},{"key":"e_1_2_6_3_1","unstructured":"BelkhirK BorsaP GoudetJ ChikhiL BonhommeF.1996.Genetix v3.0 logiciel sous Windows TM pour la genetique des populations. 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