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  • Tisato, VeronicaDepartment of Translational Medicine, University of Ferrara, Ferrara, Italy; LTTA Centre, University of Ferrara, Ferrara, Italy; University Strategic Centre for Studies on Gender Medicine, University of Ferrara, Ferrara, Italy (författare)

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

  • Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

  • BioMed Central (BMC),2023
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:oru-111931
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-111931URI
  • https://doi.org/10.1186/s40246-023-00562-9DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

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Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • his study was funded by Local University Grants FAR and FIRD to DG and VT.
  • 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 (r2 = 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 (Delta SLC40A1 = + 8.99 dB HL and Delta HAMP = - 6.07 dB HL). In multivariate investigations, principal component analysis (PCA) yielded PC1 (PTA, age, LINE-1, HAMP, SLC40A1) and PC2 (sex, HFEC282Y, 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.

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Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Castiglione, Alessandro,1976-Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Audiology Department(Swepub:oru)ace (författare)
  • Ciorba, AndreaDepartment of Neurosciences, University Hospital of Ferrara, Ferrara, Italy (författare)
  • Aimoni, ClaudiaDepartment of Neurosciences, University Hospital of Ferrara, Ferrara, Italy (författare)
  • Silva, Juliana AraujoDepartment of Translational Medicine, University of Ferrara, Ferrara, Italy (författare)
  • Gallo, InesDepartment of Translational Medicine, University of Ferrara, Ferrara, Italy (författare)
  • D’Aversa, ElisabettaDepartment of Translational Medicine, University of Ferrara, Ferrara, Italy (författare)
  • Salvatori, FrancescaDepartment of Translational Medicine, University of Ferrara, Ferrara, Italy (författare)
  • Bianchini, ChiaraDepartment of Neurosciences, University Hospital of Ferrara, Ferrara, Italy (författare)
  • Pelucchi, StefanoDepartment of Neurosciences, University Hospital of Ferrara, Ferrara, Italy (författare)
  • Secchiero, PaolaDepartment of Translational Medicine, University of Ferrara, Ferrara, Italy (författare)
  • Zauli, GiorgioDepartment of Environmental and Prevention Sciences, University of Ferrara, Ferrara, Italy (författare)
  • Singh, Ajay VikramDepartment of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Berlin, Germany (författare)
  • Gemmati, DonatoDepartment of Translational Medicine, University of Ferrara, Ferrara, Italy; University Strategic Centre for Studies on Gender Medicine, University of Ferrara, Ferrara, Italy; Centre Haemostasis and Thrombosis, University of Ferrara, Ferrara, Italy (författare)
  • Department of Translational Medicine, University of Ferrara, Ferrara, Italy; LTTA Centre, University of Ferrara, Ferrara, Italy; University Strategic Centre for Studies on Gender Medicine, University of Ferrara, Ferrara, ItalyInstitutionen för medicinska vetenskaper (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Human Genomics: BioMed Central (BMC)17:11473-95421479-7364

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