日本老年人群中听力损伤与编码炎症介质的基因多态性之间的关联。
The association between hearing impairment and polymorphisms of genes encoding inflammatory mediators in Japanese aged population.
机构信息
Department of Otorhinolaryngology, Aichi Medical University, Nagakute, Aichi prefecture Japan ; Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, Obu City, Aichi prefecture Japan.
Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, Obu City, Aichi prefecture Japan.
出版信息
Immun Ageing. 2014 Nov 26;11(1):18. doi: 10.1186/s12979-014-0018-4. eCollection 2014.
BACKGROUND
Aging process is accompanied by a chronic sub-clinical systemic inflammation. This study aimed to assess the association between hearing impairment and polymorphisms of genes encoding cytokines deeply-committed to the inflammatory response and immune homeostasis in an elderly Japanese population. Data were collected in the Longitudinal Study of Aging surveyed biennially between 1997 and 2010. The participants without any missing information at baseline were 1,957 individuals, and the gross accumulated number of 8,675 subjects (40-89 years of age) was analyzed. Two hearing impairment criteria were taken as the better ear pure-tone average (PTABE) greater than 25 dB and greater than 40 dB. We analyzed cumulative data using generalized estimating equations to investigate the effect of 9 polymorphisms, namely, tumor necrosis factor (TNF) α, rs1800630; TNF receptor super family (TNFRSF) 1B, rs1061624; interleukin (IL)-1A, rs1800587; IL-1B, rs16944; IL-4R, rs1801275; IL-6, rs1800796; IL-10, rs1800872; IL-1 receptor-associated kinase 1 (IRAK1), rs1059702; C reactive protein (CRP), rs1130864.
RESULTS
The odds ratios for the hearing impairment (PTABE >25 dB) risk under additive genetic model were significant in TNF-α rs1800630 and TNFRSF1B rs1061624, which were respectively 1.172 (confidence interval [CI]: 1.005-1.367), 1.211 (CI: 1.053-1.392) in model after adjustment for possible confounders. Using the criterion of PTABE >40 dB as disabling hearing impairment, the association remains significant in TNFRSF1B rs1061624, but not in TNF-α rs1800630. No other polymorphisms showed a significant association.
CONCLUSIONS
The present population-based cohort study demonstrated that TNF-α rs1800630 and TNFRSF1B rs1061624 contributed to the incremental risk of hearing impairment in the elderly. TNF-α and TNF receptor interactions play a pivotal role in the pathogenesis of the inflammatory response, and also cause programmed cell death and cell proliferation. The present observation implied the signalling cascades of TNF were involved in ear aging.
背景
衰老过程伴随着慢性亚临床全身炎症。本研究旨在评估在老年日本人群中，编码细胞因子的基因多态性与听力损伤之间的关系，这些细胞因子深度参与炎症反应和免疫稳态。数据采集于 1997 年至 2010 年间每两年进行一次的纵向老龄化研究中。在基线时没有任何缺失信息的参与者有 1957 人，共分析了 8675 名受试者（40-89 岁）的总累积数据。采用纯音平均（PTABE）大于 25dB 和大于 40dB 的较好耳作为两种听力损伤标准。我们使用广义估计方程分析累积数据，以研究 9 种多态性的影响，即肿瘤坏死因子（TNF）α，rs1800630；肿瘤坏死因子受体超家族（TNFRSF）1B，rs1061624；白细胞介素（IL）-1A，rs1800587；IL-1B，rs16944；IL-4R，rs1801275；IL-6，rs1800796；IL-10，rs1800872；IL-1 受体相关激酶 1（IRAK1），rs1059702；C 反应蛋白（CRP），rs1130864。
结果
在调整了可能的混杂因素后，TNF-α rs1800630 和 TNFRSF1B rs1061624 在加性遗传模型下，听力损伤（PTABE >25dB）风险的优势比具有统计学意义，分别为 1.172（置信区间[CI]：1.005-1.367）和 1.211（CI：1.053-1.392）。使用 PTABE >40dB 作为失能性听力损伤的标准，TNFRSF1B rs1061624 仍存在显著相关性，但 TNF-α rs1800630 则不具有相关性。其他多态性没有表现出显著相关性。
结论
本基于人群的队列研究表明，TNF-α rs1800630 和 TNFRSF1B rs1061624 导致老年人听力损伤的风险增加。TNF-α 和 TNF 受体的相互作用在炎症反应的发病机制中起着关键作用，同时也导致程序性细胞死亡和细胞增殖。本研究观察到 TNF 信号通路可能参与了耳部衰老。
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