Bouzid Amal, Tekari Adel, Jbeli Fida, Chakroun Amine, Hansdah Kirtal, Souissi Amal, Singh Neha, Mosrati Mohamed Ali, Achour Imen, Ghorbel Abdelmonem, Charfeddine Ilhem, Ramchander Puppala Venkat, Masmoudi Saber
Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, University of Sfax, Road Sidi Mansour Km 6, BP 1177, 3018, Sfax, Tunisia.
Department of Otorhinolaryngology, Habib Bourguiba Teaching Hospital, University of Sfax, Avenue El Ferdaws, 3029, Sfax, Tunisia.
BMC Med Genet. 2020 Jun 3;21(1):122. doi: 10.1186/s12881-020-01036-8.
Otosclerosis (OTSC) is among the most common causes of a late-onset hearing loss in adults and is characterized by an abnormal bone growth in the otic capsule. Alteration in the osteoprotegerin (OPG) expression has been suggested in the implication of OTSC pathogenesis.
A case-control association study of rs2228568, rs7844539, rs3102734 and rs2073618 single nucleotide polymorphisms (SNPs) in the OPG gene was performed in a Tunisian-North African population composed of 183 unrelated OTSC patients and 177 healthy subjects. In addition, a multilocus association and a meta-analysis of existing studies were conducted.
Rs3102734 (p = 0.013) and rs2073618 (p = 0.007) were significantly associated with OTSC, which were predominantly detected in females after multiple corrections. Among the OPG studied SNPs, the haplotypes A-A-C-G (p = 0.0001) and A-A-C-C (p = 0.0004) were significantly associated with OTSC in females. Multilocus association revealed that the SNPs: rs2073618 in OPG, rs1800472 in TGFβ1, rs39335, rs39350 and rs39374 in RELN, and rs494252 in chromosome 11 showed significant OTSC-associated alleles in Tunisian individuals. In addition, meta-analysis of the rs2073618 SNP in Tunisian, Indian and Italian populations revealed evidence of an association with OTSC (OR of 0.826, 95% CI [0.691-0.987], p = 0.035).
Our findings suggest that rs3102734 and rs2073618 variants are associated with OTSC in North African ethnic Tunisian population. Meta-analysis of the rs2073618 in three different ethnic population groups indicated an association with OTSC.
耳硬化症（OTSC）是成人迟发性听力损失的最常见原因之一，其特征是耳囊内出现异常的骨质生长。有研究表明骨保护素（OPG）表达的改变与耳硬化症的发病机制有关。
在一个由183名无亲缘关系的耳硬化症患者和177名健康受试者组成的突尼斯-北非人群中，对OPG基因中的rs2228568、rs7844539、rs3102734和rs2073618单核苷酸多态性（SNP）进行病例对照关联研究。此外，还进行了多位点关联分析和现有研究的荟萃分析。
Rs3102734（p = 0.013）和rs2073618（p = 0.007）与耳硬化症显著相关，在多次校正后，这些关联主要在女性中检测到。在研究的OPG SNP中，单倍型A-A-C-G（p = 0.0001）和A-A-C-C（p = 0.0004）在女性中与耳硬化症显著相关。多位点关联分析显示，SNP：OPG中的rs2073618、TGFβ1中的rs1800472、RELN中的rs39335、rs39350和rs39374以及11号染色体上的rs494252在突尼斯个体中显示出与耳硬化症相关的显著等位基因。此外，对突尼斯、印度和意大利人群中rs2073618 SNP的荟萃分析显示有证据表明其与耳硬化症相关（OR为0.826，95% CI [0.691 - 0.987]，p = 0.035）。
我们的研究结果表明，rs3102734和rs2073618变体与突尼斯北非族裔人群的耳硬化症相关。对三个不同种族人群组中rs2073618的荟萃分析表明其与耳硬化症相关。
