Association between NF-E2-related factor 2 polymorphism and age-related hearing loss in the general Japanese population from the Iwaki health promotion project

Acta Otolaryngol. 2025 Jan;145(1):36-42. doi: 10.1080/00016489.2024.2435459. Epub 2024 Dec 6.

Abstract

Background: Single-nucleotide polymorphisms (SNPs) of the NF-E2-related factor 2 (NRF2) gene might be associated with several diseases. In the animal models, NRF2 has been reported to be associated with the age-related hearing loss (ARHL). However, the effect of NRF2 SNPs on ARHL in the general population has not been reported.

Objectives: This study aimed to evaluate the effect of NRF2 SNP-617 on ARHL in the general Japanese population.

Methods: This study included participants from the Iwaki Health Promotion Project. The genotypes of NRF2 SNP-617 were determined via whole-genome sequencing, and the hearing level of the CC homozygote + CA heterozygote carrier group was compared with that of the AA homozygote carrier group.

Results: Among the 306 CC+CA and 31 AA group male subjects, 22 (7.2%) and six (19.4%), respectively, had hearing loss, with a significant difference. Multiple logistic regression analysis showed that the risk of hearing loss in the male subjects was significantly higher in the AA group than that in the CC+CA group (p = .031, odds ratio = 3.437, 95% confidence interval = 1.116-10.580).

Conclusion: The genotypes of NRF2 SNP-617 AA carriers were significantly associated with the development of ARHL among the males aged 30-59 years.

Keywords: Iwaki Health Promotion Project; NRF2 SNP-617; age-related hearing loss; general population; reactive oxygen species.

MeSH terms

  • Adult
  • Aged
  • East Asian People
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Health Promotion
  • Hearing Loss / epidemiology
  • Hearing Loss / genetics
  • Humans
  • Japan / epidemiology
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2* / genetics
  • Polymorphism, Single Nucleotide*
  • Presbycusis / epidemiology
  • Presbycusis / genetics

Substances

  • NF-E2-Related Factor 2
  • NFE2L2 protein, human