title: Genetic variants in RELN are associated with otosclerosis in a non-European population from Tunisia.
abstract: Otosclerosis is a common form of conductive hearing loss, caused by an abnormal bone remodelling in the otic capsule. Both environmental and genetic factors have been implicated in the etiology of this disease. A recent genome wide association study identified two regions associated with otosclerosis, one on chr7q22.1, located in the RELN gene, and one on chr11q13.1. A second study in four European populations has replicated the association of the RELN gene with otosclerosis. To investigate the association of these loci with otosclerosis in a non-European population, we tested 11 SNPs from the two regions in 149 unrelated Tunisian patients and 152 controls. Four SNPs were significantly associated with otosclerosis. Three SNPs are located in the RELN region and the last one is located in the region on chromosome 11. We also observed a significant interaction with gender for rs3914132. This suggests an influence of sex on the association of RELN with otosclerosis. A meta-analysis showed that the disease-associated alleles in the Tunisian sample are the same as in all previously reported associations. Our study provides additional evidence implicating RELN in the development of otosclerosis. Additional functional studies should determine the role of RELN in the physiopathology of this disease.
authors.affiliation: Unité Cibles pour le Diagnostic et la Thérapie, Centre de Biotechnologie de Sfax, Tunisie.
authors.forename: Ayda
authors.initials: A
authors.lastname: Khalfallah
authors.forename: Isabelle
authors.initials: I
authors.lastname: Schrauwen
authors.forename: Malek
authors.initials: M
authors.lastname: Mnaja
authors.forename: Erik
authors.initials: E
authors.lastname: Fransen
authors.forename: Imed
authors.initials: I
authors.lastname: Lahmar
authors.forename: Megan
authors.initials: M
authors.lastname: Ealy
authors.forename: Leila
authors.initials: L
authors.lastname: Dhouib
authors.forename: Hammadi
authors.initials: H
authors.lastname: Ayadi
authors.forename: Ilhem
authors.initials: I
authors.lastname: Charfedine
authors.forename: Nabil
authors.initials: N
authors.lastname: Driss
authors.forename: Abdelmonem
authors.initials: A
authors.lastname: Ghorbel
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: Saber
authors.initials: S
authors.lastname: Masmoudi
authors.forename: Guy
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010040:Otosclerosis / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D012727:Sex Characteristics; D014416:Tunisia
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases