ABSTRACT
BACKGROUND: Otitis media (OM) is a middle ear inflammatory complex disorder involving genetic and environmental factors. It onsets during childhood and often recurs and perplexes in genetically susceptible patients. Previously, murine models had shown the association of ISL LIM homeobox 1 (ISL1) gene with otitis media with effusion. AIM: To investigate the association of ISL1 genetic variants with otitis media. SUBJECTS AND METHODS: A total of 285 cases and 277 controls were recruited for the study. The entire coding region of ISL1 gene was genotyped using Sanger sequencing or single-strand conformation polymorphism methods. Genotype, haplotype, in silico analysis, and linkage disequilibrium analysis were performed. RESULTS: The variants rs2303751 (c.504A>G) and rs121913540 (c.513G>A) were associated with OM, and the OR (95%CI) was 0.74 (0.57-0.95) and 0.43 (0.20-0.91), respectively. Besides, the rs2303751 AA genotype was associated with elevated eosinophil numbers in OM when compared to controls. The 5 SNP haplotype analysis of SNPs c.-492A>G, c.504A>G, c.513G>A, c.576C>T, and c.*651A>T revealed A-A-G-C-A to be a risk haplotype in females whereas the 3 SNP haplotype analysis of SNPs c.504A>G, c.513G>A, and c.567C>T suggested G-A-C as protective and A-G-C to be a risk haplotype for otitis media. CONCLUSION: Ours is the first report which shows a significant association of ISL1 variants (rs2303751 and rs121913540) with hearing-related disorder like otitis media in humans. These results implicate the possible role of ISL1 gene in the etiopathology of otitis media. The replication of the study in other ethnic populations may strengthen our findings.
