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Publications

Journal Article Research Support, Non-U.S. Gov't Epublish 15 citations

PubMed: 38098073 DOI: 10.1186/s40246-023-00562-9

LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL).

Hum Genomics 17(1):112

Authors: Veronica Tisato, Alessandro Castiglione, Andrea Ciorba, Claudia Aimoni, Juliana Araujo Silva, Ines Gallo, Elisabetta D'Aversa, Francesca Salvatori, Chiara Bianchini, Stefano Pelucchi, Paola Secchiero, Giorgio Zauli, Ajay Vikram Singh, Donato Gemmati

Affiliations

  • Department of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
  • LTTA Centre, University of Ferrara, 44121, Ferrara, Italy.
  • University Strategic Centre for Studies on Gender Medicine, University of Ferrara, 44121, Ferrara, Italy.
  • Audiology Department, Örebro University Hospital, 70210, Örebro, Sweden.
  • Department of Neurosciences, University Hospital of Ferrara, 44121, Ferrara, Italy.
  • Department of Environmental and Prevention Sciences, University of Ferrara, 44121, Ferrara, Italy.
  • Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), 10589, Berlin, Germany.
  • Department of Translational Medicine, University of Ferrara, 44121, Ferrara, Italy.
  • University Strategic Centre for Studies on Gender Medicine, University of Ferrara, 44121, Ferrara, Italy.
  • Centre Haemostasis and Thrombosis, University of Ferrara, 44121, Ferrara, Italy.

Abstract

BACKGROUND

Sudden sensorineural hearing loss (SSNHL) is an abrupt loss of hearing, still idiopathic in most of cases. Several mechanisms have been proposed including genetic and epigenetic interrelationships also considering iron homeostasis genes, ferroptosis and cellular stressors such as iron excess and dysfunctional mitochondrial superoxide dismutase activity.

RESULTS

We investigated 206 SSNHL patients and 420 healthy controls for the following genetic variants in the iron pathway: SLC40A1 - 8CG (ferroportin; FPN1), HAMP - 582AG (hepcidin; HEPC), HFE C282Y and H63D (homeostatic iron regulator), TF P570S (transferrin) and SOD2 A16V in the mitochondrial superoxide dismutase-2 gene. Among patients, SLC40A1 - 8GG homozygotes were overrepresented (8.25% vs 2.62%; P = 0.0015) as well SOD2 16VV genotype (32.0% vs 24.3%; P = 0.037) accounting for increased SSNHL risk (OR = 3.34; 1.54-7.29 and OR = 1.47; 1.02-2.12, respectively). Moreover, LINE-1 methylation was inversely related (r = 0.042; P = 0.001) with hearing loss score assessed as pure tone average (PTA, dB HL), and the trend was maintained after SLC40A1 - 8CG and HAMP - 582AG genotype stratification (Δ = + 8.99 dB HL and Δ = - 6.07 dB HL). In multivariate investigations, principal component analysis (PCA) yielded PC1 (PTA, age, LINE-1, HAMP, SLC40A1) and PC2 (sex, HFE, SOD2, HAMP) among the five generated PCs, and logistic regression analysis ascribed to PC1 an inverse association with moderate/severe/profound HL (OR = 0.60; 0.42-0.86; P = 0.0006) and with severe/profound HL (OR = 0.52; 0.35-0.76; P = 0.001).

CONCLUSION

Recognizing genetic and epigenetic biomarkers and their mutual interactions in SSNHL is of great value and can help pharmacy science to design by pharmacogenomic data classical or advanced molecules, such as epidrugs, to target new pathways for a better prognosis and treatment of SSNHL.

MeSH

Genes, Genomics, Homeostasis, Hearing, Dna Methylation, Superoxides, Hearing Loss, Sensorineural, Sex, Genotype, Hearing Loss, Superoxide Dismutase

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