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Background . Even if various pathophysiological events have been proposed as explanations, the putative cause of sudden hearing loss remains unclear.  Objectives . To investigate and to reveal associations (if any) between the main iron-related gene variants and idiopathic sudden sensorineural hearing loss.  Study Design . Case-control study.  Materials and Methods . A total of 200 sudden sensorineural hearing loss patients (median age 63.65 years; range 10–92) were compared with 400 healthy control subjects. The following genetic variants were investigated: the polymorphism c.−8CG in the promoter of the ferroportin gene (FPN1;  SLC40A1 ), the two isoforms C1 and C2 (p.P570S) of the transferrin protein ( TF ), the amino acidic substitutions p.H63D and p.C282Y in the hereditary hemochromatosis protein ( HFE ), and the polymorphism c.–582AG in the promoter of the  HEPC  gene, which encodes the protein hepcidin (HAMP).  Results . The homozygous genotype c.−8GG of the  SLC40A1  gene revealed an OR for ISSNHL risk of 4.27 (CI 95%, 2.65–6.89;  P  = 0.001), being overrepresented among cases.  Conclusions . Our study indicates that the homozygous genotype  FPN1  −8GG was significantly associated with increased risk of developing sudden hearing loss. These findings suggest new research should be conducted in the field of iron homeostasis in the inner ear.

Sudden Sensorineural Hearing Loss and Polymorphisms in Iron Homeostasis Genes: New Insights from a Case-Control Study