Endothelin-1 Gene Polymorphism and Hearing Impairment in Elderly Japanese

Objectives/Hypothesis: To investigate the association between the Lys198Asn (G/T) polymorphism (rs5370) in the endothelin-1 gene (EDN1) and hearing impairment in middle-aged and elderly Japanese. Study Design: Longitudinal study. Methods: Data were collected from community-dwelling Japanese adults who participated in the Longitudinal Study of Aging biennially between 1997 and 2006. The participants at baseline were 2,231 adults aged 40 years to 79 years. An average hearing threshold level of 25 dB or better in the better ear for frequencies 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz was defined as no hearing impairment. Using generalized estimating equations to treat repeated observations within subjects, 7,097 cumulative data were analyzed to assess the association between hearing status and the EDN1 G/T polymorphism with adjustment for age, sex, histories of ear disease, occupational noise exposure, heart disease, hypertension, and body mass index under additive, dominant, and recessive genetic models. Results: Comparison with wild-type homozygotes (GG), heterozygotes, and mutant homozygotes (GT/TT) showed a positive association with hearing impairment after adjustment for age in model 1 (odds ratio [OR] = 1.24; 95% confidence interval [CI] = 1.02-1.50; P = .033), for age and sex in model 2 (OR = 1.29; CI = 1.06-1.57; P = .0122), and for age, sex, history of ear disease, and history of occupational noise exposure in model 3 (OR = 1.31; CI = 1.07-1.60; P = .0092). The association was also significant in model 3 under the additive model. Conclusions: This study demonstrated that mutant T-allele carriers were associated with a higher risk of hearing impairment than carriers of wild-type homozygotes in middle-aged and elderly people. This result implies that endothelin-1 plays a valuable role in the cochlea.