title: Association of DSC1, a gene modulated by adrenergic stimulation, with Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a complex multifactorial disorder involving a number of genetic and environmental factors, with severe head injury consistently reported as a major non-genetic risk factor. The adrenergic activation that occurs during major trauma increases cAMP levels, therefore the cAMP signaling pathway might be involved in AD pathogenesis. Time course of candidate gene expression following adrenergic stimulation with isoproterenol was assayed in neuroblastoma cells by quantitative reverse transcription (RT)-PCR. Then, genetic association studies of polymorphisms in several of these candidate genes were performed. Association studies in two independent case-control samples showed a polymorphism in DSC1, encoding desmocollin 1--a member of the desmosomal cadherins--which modulated AD susceptibility in a gender-specific manner. These results are in accordance with the potential involvement of the adrenergic signaling pathway in AD pathogenesis.
authors.affiliation: Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (C.S.I.C.-U.A.M.), Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
authors.forename: María C
authors.initials: MC
authors.lastname: Ramos
authors.forename: Raquel
authors.initials: R
authors.lastname: Tenorio
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez-García
authors.forename: Isabel
authors.initials: I
authors.lastname: Sastre
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vilella-Cuadrada
authors.forename: Ana
authors.initials: A
authors.lastname: Frank
authors.forename: Marcel
authors.initials: M
authors.lastname: Rosich-Estragó
authors.forename: Fernando
authors.initials: F
authors.lastname: Valdivieso
authors.forename: María J
authors.initials: MJ
authors.lastname: Bullido
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D045744:Cell Line, Tumor; D051187:Desmocollins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D016015:Logistic Models; D008297:Male; D009447:Neuroblastoma; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012737:Sex Factors; D013997:Time Factors
chemical_list: D000318:Adrenergic beta-Agonists; C081560:DSC1 protein, human; D051187:Desmocollins; D012333:RNA, Messenger; D007545:Isoproterenol