title: The association between hearing impairment and polymorphisms of genes encoding inflammatory mediators in Japanese aged population.
abstract: 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.
authors.affiliation: Department of Otorhinolaryngology, Aichi Medical University, Nagakute, Aichi prefecture Japan ; Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, Obu City, Aichi prefecture Japan.
authors.forename: Yasue
authors.initials: Y
authors.lastname: Uchida
authors.affiliation: Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, Obu City, Aichi prefecture Japan.
authors.forename: Saiko
authors.initials: S
authors.lastname: Sugiura
authors.affiliation: Department of Otorhinolaryngology, Aichi Medical University, Nagakute, Aichi prefecture Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Department of Otorhinolaryngology, National Center for Geriatrics and Gerontology, Obu City, Aichi prefecture Japan ; Department of Otorhinolaryngology Cognitive and Speech Medicine, Nagoya University School of Medicine, Nagoya City, Aichi prefecture Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakashima
authors.affiliation: Department of Health and Medical Sciences, Aichi Shukutoku University, Aichi prefecture, Japan.
authors.forename: Fujiko
authors.initials: F
authors.lastname: Ando
authors.affiliation: Department for Development of Preventive Medicine, National Center for Geriatrics and Gerontology, Obu City, Aichi prefecture Japan ; Graduate School of Nutritional Sciences, Nagoya University of Arts and Sciences, Nisshin, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimokata
keywords: Age-related hearing loss; Longitudinal study; Polymorphism; TNFα