دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL)
المؤلفون: 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
المصدر: Human Genomics, Vol 17, Iss 1, Pp 1-11 (2023)
بيانات النشر: BMC, 2023.
سنة النشر: 2023
المجموعة: LCC:Medicine
LCC:Genetics
مصطلحات موضوعية: Epigenomics, Epigenetics, Epidrugs, Iron, LINE-1 methylation, Oxidative stress, Medicine, Genetics, QH426-470
الوصف: 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 2 = 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 SLC40A1 = + 8.99 dB HL and Δ HAMP = − 6.07 dB HL). In multivariate investigations, principal component analysis (PCA) yielded PC1 (PTA, age, LINE-1, HAMP, SLC40A1) and PC2 (sex, HFE C282Y , 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1479-7364
Relation: https://doaj.org/toc/1479-7364
DOI: 10.1186/s40246-023-00562-9
URL الوصول: https://doaj.org/article/c474315ce2f3488fba66371f2fa879d4
رقم الأكسشن: edsdoj.474315ce2f3488fba66371f2fa879d4
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:14797364
DOI:10.1186/s40246-023-00562-9