University of Oulu

Skarp, S., Korvala, J., Kotimäki, J., Sorri, M., Männikkö, M., & Hietikko, E. (2022). New genetic variants in cyp2b6 and slc6a support the role of oxidative stress in familial ménière’s disease. Genes, 13(6), 998.

New genetic variants in CYP2B6 and SLC6A support the role of oxidative stress in familial Ménière’s disease

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Author: Skarp, Sini1; Korvala, Johanna2; Kotimäki, Jouko3;
Organizations: 1Research Unit of Biomedicine, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland
2University of Oulu Graduate School, University of Oulu, 90220 Oulu, Finland
3Department of Otorhinolaryngology, Kainuu Central Hospital, 87300 Kajaani, Finland
4Department of Otorhinolaryngology and Head and Neck Surgery, Oulu University Hospital, 90220 Oulu, Finland
5Finland & PEDEGO Research Unit, University of Oulu, 90220 Oulu, Finland
6Infrastructure for Population Studies, Northern Finland Birth Cohorts, Faculty of Medicine, University of Oulu, 90220 Oulu, Finland
7Center for Life-Course Health Research, Faculty of Medicine, University of Oulu, Finland and Oulu City Hospital, 90220 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.9 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2022
Publish Date: 2023-02-08


The objective was to study the genetic etiology of Ménière’s disease (MD) using next-generation sequencing in three families with three cases of MD. Whole exome sequencing was used to identify rare genetic variants co-segregating with MD in Finnish families. In silico estimations and population databases were used to estimate the frequency and pathogenicity of the variants. Variants were validated and genotyped from additional family members using capillary sequencing. A geneMANIA analysis was conducted to investigate the functional pathways and protein interactions of candidate genes. Seven rare variants were identified to co-segregate with MD in the three families: one variant in the CYP2B6 gene in family I, one variant in GUSB and EPB42 in family II, and one variant in each of the SLC6A, ASPM, KNTC1, and OVCH1 genes in family III. Four of these genes were linked to the same co-expression network with previous familial MD candidate genes. Dysfunction of CYP2B6 and SLC6A could predispose to MD via the oxidative stress pathway. Identification of ASPM and KNTC1 as candidate genes for MD suggests dysregulation of mitotic spindle formation in familial MD. The genetic etiology of familial MD is heterogenic. Our findings suggest a role for genes acting on oxidative stress and mitotic spindle formation in MD but also highlight the genetic complexity of MD.

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Series: Genes
ISSN: 2073-4425
ISSN-E: 2073-4425
ISSN-L: 2073-4425
Volume: 13
Issue: 6
Article number: 998
DOI: 10.3390/genes13060998
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3125 Otorhinolaryngology, ophthalmology
Funding: This study was supported by grants from the Finnish Foundation for Ear Diseases and the Emil Aaltonen Foundation.
Copyright information: © 2022 by the authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (