Amal Bouzid1, Ibtihel Smeti1, Leila Dhouib2, Magali Roche3, Imen Achour2, Aida Khalfallah1, Abdullah Ahmed Gibriel4, Ilhem Charfeddine2, Hammadi Ayadi1, Joel Lachuer3, Abdelmonem Ghorbel2, Christine Petit5,6,7, Saber Masmoudi1. 1. a Laboratoire de Procédés de Criblage Moléculaire et Cellulaire, Centre de Biotechnologie de Sfax , Université de Sfax , Sfax , Tunisie. 2. b Service d'O.R.L, C.H.U. H. Bourguiba de Sfax , Sfax , Tunisie. 3. c Faculté de Médecine et de Pharmacie de Lyon, ISPBL, ProfileXpert-LCM , Lyon , France. 4. d Department of Biochemistry and Molecular Biology, Faculty of Pharmacy , The British University in Egypt , Cairo , Egypt. 5. e Unité de Génétique et Physiologie de l'Audition , Institut Pasteur , Paris , France. 6. f UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM) , Paris , France. 7. g Collège de France , Paris , France.
Abstract
CONTEXT: Presbycusis, an age-related hearing impairment (ARHI), represents the most common sensory disability in adults. Today, the molecular mechanisms underlying presbycusis remain unclear. This is in particular due to the fact that ARHI is a multifactorial complex disorder resulting from several genomic factors interacting with lifelong cumulative effects of: disease, diet, and environment. OBJECTIVE: Identification of novel biomarkers for presbycusis. MATERIALS AND METHODS: We selectively ascertained 18 elderly unrelated women lacking environmental and metabolic risk factors. Subsequently, we screened for methylation map changes in blood samples of women with presbycusis as compared to controls, using reduced representation bisulfite sequencing. We focused on hypermethylated cytosine bases located in gene promoters and the first two exons. To elucidate the related gene expression changes, we performed transcriptomic study using gene expression microarray. RESULTS: Twenty-seven genes, known to be expressed in adult human cochlea, were found in the blood cells to be differentially hypermethylated with significant (p < 0.01) methylation differences (>30%) and down-expressed with fold change >1.2 (FDR <0.05). Functional annotation and qRT-PCR further identified P2RX2, KCNQ5, ERBB3 and SOCS3 to be associated with the progression of ARHI. DISCUSSION AND CONCLUSION: Down-expressed genes associated with DNA hypermethylation could be used as biomarkers for understanding complex pathogenic mechanisms underlying presbycusis.
CONTEXT: Presbycusis, an age-related hearing impairment (ARHI), represents the most common sensory disability in adults. Today, the molecular mechanisms underlying presbycusis remain unclear. This is in particular due to the fact that ARHI is a multifactorial complex disorder resulting from several genomic factors interacting with lifelong cumulative effects of: disease, diet, and environment. OBJECTIVE: Identification of novel biomarkers for presbycusis. MATERIALS AND METHODS: We selectively ascertained 18 elderly unrelated women lacking environmental and metabolic risk factors. Subsequently, we screened for methylation map changes in blood samples of women with presbycusis as compared to controls, using reduced representation bisulfite sequencing. We focused on hypermethylated cytosine bases located in gene promoters and the first two exons. To elucidate the related gene expression changes, we performed transcriptomic study using gene expression microarray. RESULTS: Twenty-seven genes, known to be expressed in adult human cochlea, were found in the blood cells to be differentially hypermethylated with significant (p < 0.01) methylation differences (>30%) and down-expressed with fold change >1.2 (FDR <0.05). Functional annotation and qRT-PCR further identified P2RX2, KCNQ5, ERBB3 and SOCS3 to be associated with the progression of ARHI. DISCUSSION AND CONCLUSION: Down-expressed genes associated with DNA hypermethylation could be used as biomarkers for understanding complex pathogenic mechanisms underlying presbycusis.
Entities:
Keywords:
Age-related hearing impairment; DNA hypermethylation; biomarkers; gene expression
Authors: Rían W Manville; Jennifer van der Horst; Kaitlyn E Redford; Benjamin B Katz; Thomas A Jepps; Geoffrey W Abbott Journal: Proc Natl Acad Sci U S A Date: 2019-09-30 Impact factor: 11.205
Authors: Amal Souissi; Mariem Ben Said; Ikhlas Ben Ayed; Ines Elloumi; Amal Bouzid; Mohamed Ali Mosrati; Mehdi Hasnaoui; Malek Belcadhi; Nabil Idriss; Hassen Kamoun; Nourhene Gharbi; Abdullah A Gibriel; Abdelaziz Tlili; Saber Masmoudi Journal: J Adv Res Date: 2021-01-12 Impact factor: 10.479