Single‐nucleotide polymorphisms in the COL1A1 regulatory regions are associated with otosclerosis

W Chen; N C Meyer; M J McKenna; M Pfister; D J McBride; K Fukushima; M Thys; G V Camp; RJH Smith

doi:10.1111/j.1399-0004.2007.00794.x

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Single‐nucleotide polymorphisms in the COL1A1 regulatory regions are associated with otosclerosis

Journal article

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Single‐nucleotide polymorphisms in the COL1A1 regulatory regions are associated with otosclerosis

W Chen, N C Meyer, M J McKenna, M Pfister, D J McBride, K Fukushima, M Thys, G V Camp and RJH Smith

Clinical genetics, Vol.71(5), pp.406-414

05/2007

DOI: 10.1111/j.1399-0004.2007.00794.x

PMID: 17489845

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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 α1(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.

Osteoporosis

COL1A1

stapes

control study

otosclerosis

hearing loss

Case Report

Details

Title: Subtitle: Single‐nucleotide polymorphisms in the COL1A1 regulatory regions are associated with otosclerosis
Creators: W Chen
N C Meyer
M J McKenna
M Pfister
D J McBride
K Fukushima
M Thys
G V Camp
RJH Smith
Resource Type: Journal article
Publication Details: Clinical genetics, Vol.71(5), pp.406-414
DOI: 10.1111/j.1399-0004.2007.00794.x
PMID: 17489845
NLM abbreviation: Clin Genet
ISSN: 0009-9163
eISSN: 1399-0004
Publisher: Blackwell Publishing Ltd; Oxford, UK
Number of pages: 9
Language: English
Date published: 05/2007
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006342502771

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