{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:21:52Z","timestamp":1777580512269,"version":"3.51.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T00:00:00Z","timestamp":1369267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,12,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>\u2003<\/jats:title>\n                  <jats:p>Otosclerosis (OTSC) is a common form of acquired hearing loss resulting from disturbed bone remodeling in the otic capsule of the middle ear. Transforming growth factor-beta1 (TGFB1) produced by osteoblasts is the most abundant growth factor in human bone. Previous studies have shown the contribution of single-nucleotide polymorphisms (SNPs) in TGFB1 toward the risk of developing OTSC in some ethnic populations. The present study was aimed at investigating the genetic association and expression profiles of TGFB1 in OTSC patients. Two SNPs (c.\u2013800G\u2009&amp;gt;\u2009A and c.\u2013509C\u2009&amp;gt;\u2009T) in the promoter region and three SNPs (c.29T\u2009&amp;gt;\u2009C, c.74G\u2009&amp;gt;\u2009C, and c.788C\u2009&amp;gt;\u2009T) in the coding region were genotyped in 170 cases and 170 controls. The genetic association analysis revealed the significant association between c.\u2013509C\u2009&amp;gt;\u2009T (p\u2009=\u20090.0067; odds ratio [OR]\u2009=\u20091.562; 95% confidence interval [CI], 1.140\u20132.139) and OTSC. The increased minor allele \u201cT\u201d frequency in cases (0.42) compared to controls (0.31) indicates its possible role in the etiology of the disease. The minor allele frequencies for the SNPs c.\u2013800G\u2009&amp;gt;\u2009A, c.29T\u2009&amp;gt;\u2009C, and c.74G\u2009&amp;gt;\u2009C were similar among the cases (0.04, 0.47, and 0.08, respectively) and controls (0.05, 0.42, 0.07, respectively). We found that c.788C\u2009&amp;gt;\u2009T was monomorphic in this population. Interestingly, a four-locus haplotype (G-T-T-G) from these SNPs was found to be significantly associated with OTSC (p\u2009=\u20090.0077). We identified a de novo heterozygous mutation c.\u2013832G\u2009&amp;gt;\u2009A in the promoter region of TGFB1 in 1 patient. In a secondary analysis, we investigated the possibility of abnormal TGFB1 expression and irregular bone growth in OTSC by expression analysis of TGFB1 mRNA in disease tissue compared to control. We found relatively increased expression of TGFB1 mRNA in the stapes tissues of cases compared to controls (p\u2009=\u20090.0057). In conclusion, this study identified a risk variant c.\u2013509C\u2009&amp;gt;\u2009T and a risk haplotype G-T-T-G in the TGFB1 gene that contribute toward the susceptibility to OTSC. \u00a9 2013 American Society for Bone and Mineral Research.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/jbmr.1991","type":"journal-article","created":{"date-parts":[[2013,5,23]],"date-time":"2013-05-23T13:38:58Z","timestamp":1369316338000},"page":"2490-2497","source":"Crossref","is-referenced-by-count":17,"title":["Genetic Association and Gene Expression Profiles of TGFB1 and the Contribution of TGFB1 to Otosclerosis Susceptibility"],"prefix":"10.1093","volume":"28","author":[{"given":"Saurabh","family":"Priyadarshi","sequence":"first","affiliation":[{"name":"Institute of Life SciencesChandrasekharpurBhubaneswarIndia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinmay Sundar","family":"Ray","sequence":"additional","affiliation":[{"name":"Department of Ear, Nose, and Throat (ENT)Shrirama Chandra Bhanj (SCB) Medical CollegeCuttackIndia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khirod Chandra","family":"Panda","sequence":"additional","affiliation":[{"name":"Ear, Nose, and Throat (ENT) UnitCapital Hospital, Unit VIBhubaneswarIndia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashim","family":"Desai","sequence":"additional","affiliation":[{"name":"Dr. ABR Desai Ear, Nose, and Throat (ENT) Clinic and Research CenterMumbaiIndia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soumya Ranjan","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine & Toxicology (FMT)Shrirama Chandra Bhanj (SCB) Medical CollegeCuttackIndia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narayan Chandra","family":"Biswal","sequence":"additional","affiliation":[{"name":"Department of Ear, Nose, and Throat (ENT)Shrirama Chandra Bhanj (SCB) Medical CollegeCuttackIndia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Puppala Venkat","family":"Ramchander","sequence":"additional","affiliation":[{"name":"Institute of Life SciencesChandrasekharpurBhubaneswarIndia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2013,5,23]]},"reference":[{"key":"2024020318324367700_jbmr1991-bib-0001","first-page":"E1005","article-title":"Parathyroid hormone-parathyroid hormone-related peptide receptor expression and function in otosclerosis","volume":"277","author":"Grayeli","year":"1999","journal-title":"Am J Physiol."},{"key":"2024020318324367700_jbmr1991-bib-0002","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.heares.2009.07.002","article-title":"The genetics of otosclerosis","volume":"266","author":"Ealy","year":"2010","journal-title":"Hear 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