부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1399-0004.2007.00794.x Byline: W Chen (a,b), NC Meyer (a), MJ McKenna (c,d), M Pfister (e), DJ McBride (f), K Fukushima (g), M Thys (h), GV Camp (h), RJH Smith (a,b) Keywords: case; control study; COL1A1; hearing loss; osteoporosis; otosclerosis; stapes Abstract: Otosclerosis (MIM 166800) has a prevalence of 0.2-1% among white adults, making it the single most common cause of hearing impairment in this ethnic group. Although measles virus, hormones, human leukocyte antigen alleles and genetic factors have been implicated in the development of otosclerosis, its etiology remains unknown. In a focused effort to identify genetic factors in otosclerosis, we have mapped four disease loci (MIM 166800/605727/608244/608787); however, cloning the disease-causing genes in these intervals has not been successful. Here, we used a case-control study design to investigate the association between collagen type I genes and otosclerosis. We identified susceptibility and protective haplotypes in COL1A1 that are significantly associated with otosclerosis in the Caucasian population. These haplotypes alter reporter gene activity in an osteoblast cell line by affecting binding of transcription factors to cis-acting elements. Our data suggest that increased amounts of collagen [alpha]1(I) homotrimers are causally related to the development of otosclerosis. Consistent with this hypothesis, mouse mutants homozygous for a Col1a2 frameshift mutation on a C57BL/6J background that deposit only homotrimeric type I collagen have hearing loss. Author Affiliation: (a)Molecular Otolaryngology Research Laboratories of the Department of Otolaryngology (b)Interdepartmental Genetics PhD Program, The University of Iowa, Iowa City, IA, USA (c)Department of Otology and Laryngology, Harvard Medical School (d)Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USA (e)Department of Otolaryngology, University Hospital Tubingen, Tubingen, Germany (f)Department of Medicine, University of Maryland, Baltimore, MD, USA (g)Department of Otolaryngology - Head and Neck Surgery, Okayama University Graduate School of Medicine, Okayama, Okayama 700-8558, Japan (h)Department of Medical Genetics, University of Antwerp, Belgium Article History: Received 26 November 2006, revised and accepted for publication 9 February 2007 Article note: Richard J.H., Smith, Department of Otolaryngology, 200 Hawkins Drive - 21151 PFP, The, University of Iowa, Iowa City, IA 52242, USA., Tel.: +319-356-3612; fax: +319-356-4108; e-mail: richard-smith@uiowa.edu