Association of COL1A1 and TGFB1 Polymorphisms with Otosclerosis in a Tunisian Population

Abstract

SummaryOtosclerosis is a condition characterized by an abnormal bone metabolism in the otic capsule, resulting in conductive and/or sensorineural hearing loss. Otosclerosis is a common disorder in which genes play an important role. Case-control association studies have implicated several genes in the abnormal bone metabolism associated with otosclerosis: COL1A1, TGFB1, BMP2, and BMP4. To investigate the association of these genes with otosclerosis in the Tunisian population, we examined nine single nucleotide polymorphisms (SNPs) in 159 unrelated otosclerosis patients and 155 unrelated controls. We found an association of rs11327935 in COL1A1 with otosclerosis that was shown to be sex specific. The coding polymorphism T263I in TGFB1 was also associated with otosclerosis in the Tunisian population. The effect sizes of both the associations were consistent with previous studies, as the same effect was found in all cases. The association of BMP2 and BMP4 was not significant. However, a trend towards association was found for the BMP4 gene that was consistent with earlier reports. In conclusion, this study replicates and strengthens the evidence for association between polymorphisms of COL1A1 and TGFB1 in the genetic aetiology of otosclerosis.

Genetic Association and Altered Gene Expression of Osteoprotegerin in Otosclerosis Patients

“…Scanning these loci has not identified any causative genes to date. In parallel, genetic association studies were carried out and showed the association of OTSC with polymorphisms in the COL1A1, TGFB1, BMP2, BMP4, and RELN genes in multiple populations (McKenna et al, 1998;Thys et al, 2007a;Schrauwen et al, 2008;Schrauwen et al, 2009;Khalfallah et al, 2010;Khalfallah et al, 2011;Priyadarshi et al, 2013). Gene expression profiling of disease tissue compared to controls has been suggested as a method to investigate the genetic basis of complex disorders (Xiong et al, 2012).…”

“…Several association studies have been performed to determine the genetic contributors for sporadic forms of OTSC. These studies have shown the association of OTSC with polymorphisms in the COL1A1 (MIM 120150), TGFB1 (MIM 190180), BMP2 (MIM 112261), BMP4 (MIM 112262), and RELN (MIM 600514) genes (McKenna et al, 1998;Thys et al, 2007a;Schrauwen et al, 2008;Schrauwen et al, 2009;Khalfallah et al, 2010;Khalfallah et al, 2011;Priyadarshi et al, 2013;Ealy et al, 2014). Some of the studies failed to replicate these associations due to small sample size or different ethnicity (Tshifularo & Joseph, 2008;Priyadarshi et al, 2010;Iossa et al, 2013).…”

Genetic Association and Gene Expression Profiles of TGFB1 and the Contribution of TGFB1 to Otosclerosis Susceptibility

“…The identification of candidate genes through genetic association studies is the method of choice for investigating the genetic basis of complex traits, and replication of these findings is essential for establishing the credibility of such results. In this replication study, a comprehensive investigation of TGFB1 polymorphisms was rigorously done to evaluate the positive findings from previous reports . TGFB1 plays an important role in cell growth and differentiation in a wide variety of cell types.…”

“…Several common polymorphisms in the TGFB1 gene with possible functional significance in the regulation of transcriptional activity have been reported. An association of TGFB1 polymorphism c.788C > T has been investigated with OTSC . The functional analysis has shown a higher activity of the causative allele c.788T than the wild‐type allele .…”

“…The coding region polymorphisms c.29T > C and c.74G > C located in the signal peptide sequence of the TGFB1 precursor encoding nonsynonymous amino acid substitutions have been associated with elevated TGFB1 serum levels . The c.788C > T polymorphism located within the cleaved part of TGFB1 was found to be significantly associated with OTSC . The activity of the c.788T allele was detected to be higher than the wild‐type allele …”