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.

中文翻译：

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骨保护素基因多态性和耳硬化症：一项额外的遗传关联研究，多位点相互作用和荟萃分析。

耳硬化症（OTSC）是成年人迟发性听力丧失的最常见原因之一，其特征是耳囊中的骨骼异常生长。骨保护素（OPG）表达的改变已经暗示了OTSC发病机理。在由183名无关OTSC患者和177名健康受试者组成的突尼斯-北非人群中，进行了OPG基因中rs2228568，rs7844539，rs3102734和rs2073618单核苷酸多态性（SNPs）的病例对照研究。此外，进行了多基因座关联和对现有研究的荟萃分析。Rs3102734（p = 0.013）和rs2073618（p = 0.007）与OTSC显着相关，这是在多次校正后女性中主要检测到的。在OPG研究的SNP中，单型AACG（p = 0。0001）和AACC（p = 0.0004）与女性OTSC显着相关。多基因座关联显示，SNPs：OPG中的rs2073618，TGFβ1中的rs1800472，RELN中的rs39335，rs39350和rs39374和11号染色体上的rs494252在突尼斯个体中显示出显着的OTSC相关等位基因。此外，对突尼斯人，印度人和意大利人rs2073618 SNP的荟萃分析揭示了与OTSC相关的证据（OR为0.826，95％CI [0.691-0.987]，p = 0.035）。我们的发现表明，rs3102734和rs2073618变体与北非突尼斯族人口中的OTSC相关。对三个不同种族人群中rs2073618的荟萃分析表明与OTSC相关。TGFβ1中的rs1800472，RELN中的rs39335，rs39350和rs39374和11号染色体上的rs494252在突尼斯个体中显示出明显的OTSC相关等位基因。此外，对突尼斯人，印度人和意大利人rs2073618 SNP的荟萃分析揭示了与OTSC相关的证据（OR为0.826，95％CI [0.691-0.987]，p = 0.035）。我们的发现表明，rs3102734和rs2073618变体与北非突尼斯族人口中的OTSC相关。对三个不同种族人群中rs2073618的荟萃分析表明与OTSC相关。TGFβ1中的rs1800472，RELN中的rs39335，rs39350和rs39374以及11号染色体中的rs494252在突尼斯个体中显示出明显的OTSC相关等位基因。此外，对突尼斯人，印度人和意大利人rs2073618 SNP的荟萃分析揭示了与OTSC相关的证据（OR为0.826，95％CI [0.691-0.987]，p = 0.035）。我们的发现表明，rs3102734和rs2073618变体与北非突尼斯族人口中的OTSC相关。对三个不同种族人群中rs2073618的荟萃分析表明与OTSC相关。印度和意大利人口揭示了与OTSC相关的证据（OR为0.826，95％CI [0.691-0.987]，p = 0.035）。我们的发现表明，rs3102734和rs2073618变体与北非突尼斯族人口中的OTSC相关。对三个不同种族人群中rs2073618的荟萃分析表明与OTSC相关。印度和意大利人口揭示了与OTSC相关的证据（OR为0.826，95％CI [0.691-0.987]，p = 0.035）。我们的发现表明，rs3102734和rs2073618变体与北非突尼斯族人口中的OTSC相关。对三个不同种族人群中rs2073618的荟萃分析表明与OTSC相关。