Molecular Genetic Analysis of Ménière's Disease


Ménière's disease (MD) is an inner ear disease characterised by tinnitus, vertigo and sensorineural hearing loss. The exact aetiology of MD is unknown but it is generally considered as a multifactorial disease. The role of genetic factors in the development of MD has been well documented. Familial clustering of MD has been observed in several studies and the proportion of familial cases is estimated to be 5–23.5%. Single locus on chromosome 12p12.3 has been reported in Swedish MD families. In addition, several inconclusive candidate‐gene analyses have been performed. At the moment, knowledge of genetic factors associated with MD is modest. Molecular genetic study of MD is complicated by genetic and clinical heterogeneity and diagnostic challenges. However, modern genetics may be useful in discovering new pathways associated with the pathophysiology of MD in the future.

Key Concepts:

  • The knowledge of genetic factors associated with MD is currently modest.

  • Genetic and clinical heterogeneity, diagnostic challenges, multifactorial origin and late onset of MD create challenges to the molecular genetic analysis of the disease.

  • Family‐based studies may assist to reduce genetic and phenotypic heterogeneity to identify molecular mechanisms or pathways involved in the pathogenesis of MD.

  • Candidate‐gene analysis is an ineffective way to study the genetics of MD and future genetic studies should emphasise the usage of linkage analyses and next‐generation sequencing as well as studying epigenetic pathways.

  • A strong interdisciplinary research environment is needed to successfully study molecular genetics of MD. Combined efforts of highly skilled otologists, geneticists and statisticians are needed to overcome the difficulties in the molecular genetic analyses of MD. To achieve power for genetic studies, a greater number of subjects are needed. This shortcoming may be corrected by an international cooperation between study groups.

Keywords: Meniere's disease; genetics; familial; multifactorial; candidate‐gene analysis; linkage analysis; next‐generation sequencing


AAO‐HNS (1995) Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy in Ménière's disease. American Academy of Otolaryngology‐Head and Neck Foundation, Inc. Otolaryngology‐Head and Neck Surgery 113(3): 181–185.

Alexander TH and Harris JP (2010) Current epidemiology of Ménière's syndrome. Otolaryngologic Clinics of North America 43(3): 965–970.

Anderson JP and Harris JP (2001) Impact of Ménière's disease on quality of life. Otology and Neurotology 22(6): 888–894.

Arweiler DJ, Jahnke K and Grosse‐Wilde H (1995) Ménière disease as an autosome dominant hereditary disease. Laryngorhinootologie 74(8): 512–515.

Arweiler‐Harbeck D, Horsthemke B, Jahnke K and Hennies HC (2011) Genetic aspects of familial Ménière's disease. Otology and Neurotology 32(4): 695–700.

Belinchon A, Perez‐Garrigues H and Tenias JM (2012) Evolution of symptoms in Ménière's disease. Audiology and Neurotology 17(2): 126–132.

Bemshad MJ, Ng SB, Bigham AW et al. (2011) Exome sequencing as a tool for Mendelian disease gene discovery. Nature Reviews Genetics 12(11): 745–755.

Birgerson L, Gustavson KH and Stahle J (1987) Familial Ménière's disease: a genetic investigation. American Journal of Otolaryngology 8(4): 323–326.

Campbell CA, Della Santina CC, Meyer NC et al. (2010) Polymorphisms in KCNE1 or KCNE3 are not associated with Ménière disease in the Caucasian population. American Journal of Medical Genetics Part A 152A(1): 67–74.

Candreia C, Schmuziger N and Gurtler N (2010) Molecular analysis of aquaporin genes 1 to 4 in patients with Ménière's disease. Cellular Physiology and Biochemistry 26(4–5): 787–792.

Doi K, Sato T, Kuramasu T et al. (2005) Ménière's disease is associated with single nucleotide polymorphisms in the human potassium channel genes, KCNE1 and KCNE3. ORL; Journal for Oto‐rhino‐laryngology and its Related Specialties 67(5): 289–293.

Ealy M and Smith RJ (2010) The genetics of otosclerosis. Hearing Research 266(1–2): 70–74.

Eckhard A, Gleiser C, Arnold H et al. (2012) Water channel proteins in the inner ear and their link to hearing impairment and deafness. Molecular Aspects of Medicine 33(5–6): 612–637.

Fransen E and Van Camp G (1999) The COCH gene: a frequent cause of hearing impairment and vestibular dysfunction? British Journal of Audiology 33(5): 297–302.

Friedman TB, Schultz JM, Ahmed ZM, Tsilou ET and Brewer CC (2011) Usher syndrome: hearing loss with vision loss. Advances in Oto‐Rhino‐Laryngology 70: 56–65.

Fritz T, Niederneiter L, Adolph T, Blumberg RS and Kaser A (2011) Crohńs disease: NOD2, autophagy and ER stress converge. Gut 60(11): 1580–1588.

Frykholm C, Larsen HC, Dahl N et al. (2006) Familial Ménière's disease in five generations. Otology and Neurotology 27(5): 681–686.

Fung K, Xie Y, Hall SF, Lillicrap DP and Taylor SA (2002) Genetic basis of familial Ménière's disease. Journal of Otolaryngology 31(1): 1–4.

Furuta T, Teranishi M, Uchida Y et al. (2011) Association of interleukin‐1 gene polymorphisms with sudden sensorineural hearing loss and Ménière's disease. International Journal of Immunogenetics 38(3): 249–254.

Gabrikova D, Frykholm C, Friberg U et al. (2010) Familiar Ménière's disease restricted to 1.48 Mb on chromosome 12p12.3 by allelic and haplotype association. Journal of Human Genetics 55(12): 834–837.

Gazquez I, Lopez‐Escamez JA, Moreno A et al. (2011) Functional variants in NOS1 and NOS2A are not associated with progressive hearing loss in Ménière's disease in a European Caucasian population. DNA and Cell Biology 30(9): 699–708.

Gazquez I, Moreno A, Aran I et al. (2012) MICA‐STR A.4 is associated with slower hearing loss progression in patients with Ménière's disease. Otology and Neurotology 33(2): 223–229.

Gibney ER and Nolan CM (2010) Epigenetics and gene expression. Heredity 105: 4–13.

Greco A, Gallo A, Fusconi M et al. (2012) Ménière's disease might be an autoimmune condition? Autoimmunity Reviews 11(10): 731–738.

Hietikko E, Kotimäki J, Kentala E et al. (2011) Finnish familial Ménière disease is not linked to chromosome 12p12.3, and anticipation and cosegregation with migraine are not common findings. Genetics in Medicine 13(5): 415–420.

Hietikko E, Kotimäki J, Okuloff A, Sorri M and Männikkö M (2012) A replication study on proposed candidate genes in Ménière's disease, and a review of the current status of genetic studies. International Journal of Audiology 51(11): 841–845.

Hietikko E, Kotimäki J, Sorri M and Männikkö M (2013) High incidence of Ménière‐like symptoms in relatives of Ménière patients in the areas of Oulu University Hospital and Kainuu Central Hospital in Finland. European Journal of Medical Genetics 56(6): 279–285.

Huang Y, Teranishi M, Uchida Y et al. (2013) Association between polymorphisms in genes encoding methylenetetrahydrofolate reductase and the risk of Ménière's disease. Journal of Neurogenetics 27(1–2): 5–10.

Huppert D, Strupp M and Brandt T (2010) Long‐term course of Ménière's disease revisited. Acta Oto‐Laryngologica 130(6): 644–651.

Jirtle RL and Skinner MK (2007) Environmental epigenomics and disease susceptibility. Nature Reviews Genetics 8: 253–262.

Kawaguchi S, Hagiwara A and Suzuki M (2008) Polymorphic analysis of the heat‐shock protein 70 gene (HSPA1A) in Ménière's disease. Acta Oto‐Laryngologica 128(11): 1173–1177.

Klar J, Frykholm C, Friberg U and Dahl N (2006) A Ménière's disease gene linked to chromosome 12p12.3. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 141B(5): 463–467.

Klockars T and Kentala E (2007) Inheritance of Ménière's disease in the Finnish population. Archives of Otolaryngology – Head and Neck Surgery 133(1): 73–77.

Kotimäki J, Sorri M, Aantaa E and Nuutinen J (1999) Prevalence of Ménière disease in Finland. Laryngoscope 109(5): 748–753.

Lopez‐Escamez JA, Moreno A, Bernal M et al. (2009) Poly(ADP‐ribose) polymerase‐1 (PARP‐1) longer alleles spanning the promoter region may confer protection to bilateral Ménière's disease. Acta Oto‐Laryngologica 129(11): 1222–1225.

Lopez‐Escamez JA, Saenz‐Lopez P, Acosta L et al. (2010) Association of a functional polymorphism of PTPN22 encoding a lymphoid protein phosphatase in bilateral Ménière's disease. Laryngoscope 120(1): 103–107.

Lopez‐Escamez JA, Saenz‐Lopez P, Gazquez I et al. (2011) Polymorphisms of CD16A and CD32 Fcgamma receptors and circulating immune complexes in Ménière's disease: a case‐control study. BMC Medical Genetics 12: 2.

Lopez‐Escamez JA, Vilchez JR, Soto‐Varela A et al. (2007) HLA‐DRB1*1101 allele may be associated with bilateral Ménière's disease in southern European population. Otology and Neurotology 28(7): 891–895.

Lynch M, Cameron TL, Knight M et al. (2002) Structural and mutational analysis of antiquitin as a candidate gene for Ménière disease. American Journal of Medical Genetics 110(4): 397–399.

Merchant SN, Adams JC and Nadol JB Jr (2005) Pathophysiology of Ménière's syndrome: are symptoms caused by endolymphatic hydrops? Otology and Neurotology 26(1): 74–81.

Mhatre AN, Jero J, Chiappini I et al. (2002) Aquaporin‐2 expression in the mammalian cochlea and investigation of its role in Ménière's disease. Hearing Research 170(1–2): 59–69.

Michel O, Hess A, Su J et al. (2000) Expression of inducible nitric oxide synthase (iNOS/NOS II) in the hydropic cochlea of guinea pigs. Hearing Research 143(1–2): 23–28.

Morrison AW, Bailey ME and Morrison GA (2009) Familial Ménière's disease: clinical and genetic aspects. Journal of Laryngology and Otology 123(1): 29–37.

Nishio N, Teranishi M, Uchida Y et al. (2013) Polymorphisms in genes encoding aquaporins 4 and 5 and estrogen receptor alpha in patients with Ménière's disease and sudden sensorineural hearing loss. Life Sciences 92(10): 541–546.

Ohmen JD, White CH, Li X et al. (2013) Genetic evidence for an ethnic diversity in the susceptibility to Ménière's disease. Otology and Neurotology 34(7): 1336–1341.

Requena T, Gazquez I, Moreno A et al. (2013) Allelic variants in TLR10 gene may influence bilateral affectation and clinical course of Meniere's disease. Immunogenetics 65(5): 345–355.

Sanchez E, Lopez‐Escamez JA, Lopez‐Nevot MA et al. (2004) Absence of COCH mutations in patients with Ménière disease. European Journal of Human Genetics 12(1): 75–78.

Shearer AE, Hildebrand MS, Sloan CM and Smith RJ (2011) Deafness in the genomics era. Hearing Research 282(1–2): 1–9.

Teggi R, Lanzani C, Zagato L et al. (2008) Gly460Trp alpha‐adducin mutation as a possible mechanism leading to endolymphatic hydrops in Ménière's syndrome. Otology and Neurotology 29(6): 824–828.

Teranishi M, Uchida Y, Nishio N et al. (2012) Polymorphisms in genes involved in oxidative stress response in patients with sudden sensorineural hearing loss and Ménière's disease in a Japanese population. DNA and Cell Biology 31(10): 1555–1562.

Usami S, Takahashi K, Yuge I et al. (2003) Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo‐vestibular dysfunction, but not of Ménière's disease. European Journal of Human Genetics 11(10): 744–748.

Van Camp G and Smith R (2012) Hereditary hearing loss database. (accessed on 19 May 2013).

Vassiliou A, Vlastarakos PV, Maragoudakis P, Candiloros D and Nikolopoulos TP (2011) Ménière's disease: still a mystery disease with difficult differential diagnosis. Annals of Indian Academy of Neurology 14(1): 12–18.

Vissher PM, Brown MA, McCarthy MI and Yang J (2012) Five years of GWAS Discovery. American Journal of Human Genetics 90: 7–24.

Vrabec JT (2010) Genetic investigations of Ménière's disease. Otolaryngologic Clinics of North America 43(5): 1121–1132.

Vrabec JT, Liu L, Li B and Leal SM (2008) Sequence variants in host cell factor C1 are associated with Ménière's disease. Otology and Neurotology 29(4): 561–566.

Watanabe K, Tomiyama S, Jinnouchi K et al. (2001) Expression of inducible nitric oxide synthase (iNOS/NOS II) in the hydropic vestibule after injection of keyhole limpet hemocyanin into the endolymphatic sac of guinea pigs. Journal of Vestibular Research 11(2): 67–71.

Weiss JN, Karma A, MacLellan WR et al. (2012) ‘Good enough solutions’ and the genetics of complex diseases. Circulation Research 111(4): 493–504.

Yazdani N, Khorsandi Ashtiani MT, Zarandy MM et al. (2013) Association between MIF gene variation and Ménière's disease. International Journal of Immunogenetics (In Press).

Further Reading

1000 Genomes Project Consortium, Abecasis GR, Altshuler D et al. (2010) A map of human genome variation from population‐scale sequencing. Nature 467(7319): 1061–1073.

Cirulli ET and Goldstein DB (2010) Uncovering the roles of rare variants in common disease through whole‐genome sequencing. Nature Reviews Genetics 11: 415–425.

Sajjadi H and Paparella MM (2008) Ménière's disease. Lancet 372(9636): 406–414.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Hietikko, Elina, Kotimäki, Jouko, and Männikkö, Minna(Oct 2013) Molecular Genetic Analysis of Ménière's Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0025161]