Khalfallah Ayda, Schrauwen Isabelle, Mnaja Malek, Fransen Erik, Lahmar Imed, Ealy Megan, Dhouib Leila, Ayadi Hammadi, Charfedine Ilhem, Driss Nabil, Ghorbel Abdelmonem, Smith Richard J H, Masmoudi Saber, Van Camp Guy
Unité Cibles pour le Diagnostic et la Thérapie, Centre de Biotechnologie de Sfax, Tunisie.
Ann Hum Genet. 2010 Sep 1;74(5):399-405. doi: 10.1111/j.1469-1809.2010.00595.x. Epub 2010 Jul 14.
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.
耳硬化症是传导性听力损失的一种常见形式，由耳囊内异常的骨重塑引起。环境因素和遗传因素均与该病的病因有关。最近一项全基因组关联研究确定了与耳硬化症相关的两个区域，一个位于7号染色体q22.1，位于RELN基因内，另一个位于11号染色体q13.1。在四个欧洲人群中进行的第二项研究重复了RELN基因与耳硬化症的关联。为了在非欧洲人群中研究这些基因座与耳硬化症的关联，我们在149名无亲缘关系的突尼斯患者和152名对照中测试了来自这两个区域的11个单核苷酸多态性（SNP）。四个SNP与耳硬化症显著相关。三个SNP位于RELN区域，最后一个位于11号染色体上的区域。我们还观察到rs3914132与性别之间存在显著相互作用。这表明性别对RELN与耳硬化症的关联有影响。一项荟萃分析表明，突尼斯样本中与疾病相关的等位基因与之前所有报道的关联中的等位基因相同。我们的研究提供了更多证据表明RELN与耳硬化症的发生有关。更多的功能研究应确定RELN在该病病理生理学中的作用。
