ASSOCIATION ANALYSIS OF RELN AND BMP2 VARIANTS WITH OTOSCLEROSIS IN BULGARIA

Otosclerosis is a frequent cause of hearing impairment characterized by abnormal resorption and deposition of bone in the human otic capsule. It is a disease of complex etiopathogenesis that is caused by both environmental and genetic factors. Previous studies showed that polymorphisms in RELN and BMP2 contribute to the disease development. The goal of the current study is to evaluate the association of polymorphisms in these genes for otosclerosis development in Bulgarian patients. We have genotyped 15 polymorphisms of RELN and two of BMP2 in 66 patients with otosclerosis, 35 healthy relatives and 100 population controls by direct sequencing. Case-control association, DFAM, TDT and haplotype analysis were performed. Association between rs39395 (p = 0.019), rs3914132 (p = 0.045) in RELN and otosclerosis were observed in the TDT analysis confirming several previous reports. Some RELN haplotypes like A-T-G-A-C-T (rs28628152-rs28417410-rs39395-rs3914131-rs3914132-rs9641319), p = 0.0455, A-A-A-T-G (rs39374-rs111806849-rs28628152-rs28417410-rs39395), p = 0.0082, were more often not transmitted and might be associated with decreased risk for otosclerosis development. No significant association between BMP2 polymorphisms and otosclerosis were observed. Our study adds support to the hypothesis that RELN polymorphisms are associated with otosclerosis. The study could not confirm the association of BMP2 polymorphisms either due to small size effect or insufficient statistical power. A larger cohort of patients and controls should be studied in order to confirm the role of RELN and BMP2 polymorphisms and better characterize their contribution and size effect.