Osteoprotegerin gene polymorphisms and otosclerosis: an additional genetic association study, multilocus interaction and meta-analysis

Abstract Background Otosclerosis (OTSC) is among the most common causes of a late-onset hearing loss and alteration in the osteoprotegerin (OPG) expression was suggested in the implication of OTSC pathogenesis. A case-control association study of single nucleotide polymorphisms (SNP) in the OPG gene was performed in a Tunisian-North African population composed of 183 unrelated OTSC patients and 177 healthy subjects.Results Rs3102734 and rs2073618 were significantly associated with OTSC which were predominantly detected in females after multiple corrections. The haplotypes A-A-C-G (p = 0.0.001) and A-A-C-C (p = 0.0004) were significantly associated with OTSC suggesting a reduced risk in females. Multilocus association revealed that: rs2073618 in OPG, rs39335, rs39350 and rs39374 in RELN, rs494252 in chromosome 11 and rs1800472 in TGFβ1 showed significant OTSC-associated alleles in the Tunisian samples. In addition, meta-analysis for rs2073618 SNP in Tunisian, Indian and Italian populations revealed evidence of association of the rs2073618 polymorphism with OTSC (Odds ratios of 0.826 (95% CI [0.691–0.987], p = 0.0035)).Conclusions Our findings suggest that rs3102734 and rs2073618 variants are associated with OTSC in an additional North African ethnic Tunisian population. Meta-analysis for rs2073618 based on three ethnic population revealed evidence of association with OTSC.