LINE-1 global DNA methylation, iron homeostasis genes, sex and age in sudden sensorineural hearing loss (SSNHL).
Hum Genomics
; 17(1): 112, 2023 Dec 14.
Article
en En
| MEDLINE
| ID: mdl-38098073
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 (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 (ΔSLC40A1 = + 8.99 dB HL and ΔHAMP = - 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pérdida Auditiva Súbita
/
Pérdida Auditiva Sensorineural
Límite:
Humans
Idioma:
En
Revista:
Hum Genomics
Asunto de la revista:
GENETICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Italia