Institute of Life Sciences, Bhubaneswar, India.
Department of Ear, Nose, and Throat (ENT), Shrirama Chandra Bhanja (SCB) Medical College & Hospital, Cuttack, India.
J Clin Lab Anal. 2021 Mar;35(3):e23702. doi: 10.1002/jcla.23702. Epub 2021 Jan 21.
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.
To investigate the association of ISL1 genetic variants with otitis media.
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.
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.
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.
中耳炎（OM）是一种涉及遗传和环境因素的中耳炎症性复杂疾病。它在儿童时期发作，并且经常在遗传易感患者中复发和复杂化。以前，鼠模型已经显示 ISL LIM 同源盒 1（ISL1）基因与分泌性中耳炎有关。
研究 ISL1 遗传变异与中耳炎的关系。
共招募了 285 例病例和 277 例对照进行研究。使用 Sanger 测序或单链构象多态性方法对 ISL1 基因的整个编码区进行基因分型。进行基因型、单倍型、计算机分析和连锁不平衡分析。
rs2303751（c.504A>G）和 rs121913540（c.513G>A）的变异与 OM 相关，OR（95%CI）分别为 0.74（0.57-0.95）和 0.43（0.20-0.91）。此外，与对照组相比，rs2303751 AA 基因型与 OM 中的嗜酸性粒细胞数量升高有关。对 SNP c.-492A>G、c.504A>G、c.513G>A、c.576C>T 和 c.*651A>T 的 5 SNP 单倍型分析显示，A-A-G-C-A 是女性的风险单倍型，而 SNP c.504A>G、c.513G>A 和 c.567C>T 的 3 SNP 单倍型分析表明，G-A-C 是保护单倍型，A-G-C 是中耳炎的风险单倍型。
这是第一项表明 ISL1 变异（rs2303751 和 rs121913540）与人类听力相关疾病，如中耳炎之间存在显著关联的报告。这些结果表明 ISL1 基因可能在中耳炎的发病机制中起作用。在其他种族人群中复制这项研究可能会加强我们的发现。
