APOE and Alzheimer disease: APOE is a gene strongly associated with the neurodegenerative condition, Alzheimer's disease—with the APOE ε4 allele predisposing to susceptibility.16, 17 In contrast to the association with Alzheimer's disease, it has been reported that the APOE ε4 allele was significantly less common in the study population with hearing loss (n = 89) compared to the frequency reported in the general population, implying a protective effect.18 Interestingly, APOE has been shown to up‐regulate N‐acetyltransferase expression, suggesting that these genes may exert an epistasis effect on ARHL.19