Top

European Archives of Oto-Rhino-Laryngology

Published in:

01-02-2017 | Otology

Genetics of ion homeostasis in Ménière’s Disease

Authors: Roberto Teggi, Laura Zagato, Simona Delli Carpini, Lorena Citterio, Claudia Cassandro, Roberto Albera, Wen-Yi Yang, Jan A. Staessen, Mario Bussi, Paolo Manunta, Chiara Lanzani

Published in: European Archives of Oto-Rhino-Laryngology | Issue 2/2017

Abstract

Aim of this work was to assess the role of polymorphisms belonging to genes involved in the regulation of ionic homeostasis in Caucasian patients with Ménière Disease (MD). We recruited 155 patients with definite Ménière Disease and 186 controls (Control Group 1) without a lifetime history of vertigo, overlapping with patients for age and rate of hypertension. We validated the positive results on 413 Caucasian subjects selected from a European general population (Control Group 2). The clinical history for migraine and hypertension was collected; genomic DNA was characterized for a panel of 33 SNPs encoding proteins involved in ionic transport. We found a higher rate of migraineurs in MD subjects compared to Group 1 (46.8 vs 15.5%, p = 0.00005). Four SNPs displayed differences in MD patients compared to Group 1 controls: rs3746951 and rs2838301 in SIK1 gene, rs434082 and rs487119 in SLC8A1; the p values of Chi-squared test for genotype frequencies are 0.009, 0.023, 0.009 and 0.048, respectively. SLC8A1 gene encodes for Na⁺-Ca⁺⁺ exchanger, while SIK1 gene encodes for Salt Inducible Kinase 1, an enzyme associated with Na⁺-K⁺ ATPase function. The validation with Control Group 2 displayed that only rs3746951 and rs487119 are strongly associated to MD (p = 0.001 and p = 0.0004, respectively). These data support the hypothesis that a genetically induced dysfunction of ionic transport may act as a predisposing factors to develop MD.

Sajjadi H, Paparella MM (2008) Ménière’s disease. Lancet 372:406–414. doi:10.1016/S0140-6736(08)61161-7 CrossRefPubMed

Merchant SN, Adams JC, Nadol JB Jr (2005) Pathophysiology of Ménière’s syndrome: are symptoms caused by endolymphatic hydrops? Otol Neurotol 26:74–81. doi:10.1097/00129492-200501000-00013 CrossRefPubMed

Vrabec JT (2010) Genetic investigations of Ménière’s disease. Otolaryngol Clin North Am 43:1121–1132. doi:10.1016/j.otc.2010.05.010 CrossRefPubMed

Morrison AW, Bailey ME, Morrison GA (2009) Familial Ménière’s disease: clinical and genetic aspects. J Laryngol Otol 123:29–37. doi:10.1017/S0022215108002788 CrossRefPubMed

Friedmann I, Fraser GR, Froggatt P (1966) Pathology of the ear in the cardioauditory syndrome of Jervell and Lange–Nielsen (recessive deafness with electrocardiographic abnormalities. J Laryngol Otol 80:451–470. doi:10.1017/s002221510006552x CrossRefPubMed

Oh SK, Baek JI, Weigand KM et al (2015) A missense variant of the ATP1A2 gene is associated with a novel phenotype of progressive sensorineural hearing loss associated with migraine. Eur J Hum Genet 23:639–645. doi:10.1038/ejhg.2014.154 CrossRefPubMed

Beitz E, Kumagami H, Krippeit-Drews P, Ruppersberg JP, Schultz JE (1999) Expression pattern of aquaporin water channels in the inner ear of the rat. The molecular basis for a water regulation system in the endolymphatic sac. Hear Res 132:76–84. doi:10.1016/s0378-5955(99)00036-2 CrossRefPubMed

Knepper MA, Inoue T (1997) Regulation of aquaporin-2 water channel trafficking by vasopressin. Curr Opin Cell Biol 9:560–564. doi:10.1016/s0955-0674(97)80034-8 CrossRefPubMed

Takeda T, Takeda S, Kakigi A et al (2010) Hormonal aspects of Ménière’s disease on the basis of clinical and experimental studies. ORL J Otorhinolaryngol Relat Spec 71:1–19. doi:10.1159/000265113 CrossRefPubMed

10.

Mallur PS, Weisstuch A, Pfister M et al (2010) Aquaporin-2 and -4: single nucleotide polymorphisms in Ménière’s disease patients. Audiol Med 8:18–23. doi:10.1159/000322346 CrossRef

11.

Candreia C, Schmuziger N, Gürtler N (2010) Molecular analysis of aquaporin genes 1 to 4 in patients with Ménière’s Disease. Cell Physiol Biochem 26:787–792. doi:10.1159/000322346 CrossRefPubMed

12.

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 J Otorhinolaryngol Relat Spec 67:289–293. doi:10.1159/000089410

13.

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. Am J Med Genet A 152:67–74. doi:10.1002/ajmg.a.33114 CrossRef

14.

Teggi R, Lanzani C, Zagato L, Delli Carpini S, Manunta P, Bianchi G, Bussi M (2008) Gly460Trp alpha-adducin mutation as a possible mechanism leading to endolymphatic hydrops in Ménière’s syndrome. Otol Neurotol 29:824–828. doi:10.1097/MAO.0b013e318180a4b1 CrossRefPubMed

15.

Teggi R, Zagato L, Delli Carpini S, Messaggio E, Casamassima N, Lanzani C, Manunta P, Bussi M (2010) Endogenous ouabain in Ménière’s disease. Otol Neurotol 31:153–156. doi:10.1097/MAO.0b013e3181c0eaba CrossRefPubMed

16.

Hietikko E, Kotimaki J, Okuloff A, Sorri M, Mannikko M (2012) A replication study on proposed candidate genes in Ménière’s disease, and a review of the current status of genetic studies. Int J Audiol 51:841–845. doi:10.3109/14992027.2012.705900 CrossRefPubMed

17.

Kim SH, Park HY, Choi HS et al (2009) Functional and molecular expression of epithelial sodium channels in cultured human endolymphatic sac epithelial cells. Otol Neurotol 30:529–534. doi:10.1097/MAO.0b013e31819a8e0e CrossRefPubMed

18.

Committee on Hearing and Equilibrium (1995) Guidelines for the diagnosis and evaluation of therapy in Ménière’s disease. Otolaryngol Head Neck Surg 113:181–185. doi:10.1016/s0194-5998(95)70102-8 CrossRef

19.

Headache Classification Subcommittee of the International Headache Society (2013) The international classification of headache disorders: 3rd edn. Cephalalgia 33:629–680. doi:10.1177/0333102413485658

20.

Liu YP, Gu YM, Thijs L, Knapen MH, Salvi E, Citterio L, Petit T, Delli Carpini S, Zhang Z, Jacobs L, Jin Y, Barlassina C, Manunta P, Kuznetsova T, Verhamme P, Struijker-Boudier HA, Cusi D, Vermeer C, Staessen JA (2015) Inactive matrix Gla protein is causally related to adverse health outcomes: a Mendelian randomization study in a Flemish population. Hypertension 65:463–470. doi:10.1161/HYPERTENSIONAHA.114.04494

21.

Livak KJ (1999) Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genet Anal 14:143–149. doi:10.1016/s1050-3862(98),00019-9 CrossRefPubMed

22.

Citterio L, Simonini M, Zagato L, Salvi E, Delli Carpini S, Lanzani C, Messaggio E, Casamassima N, Frau F, D’Avila F, Cusi D, Barlassina C, Manunta (2011) Genes involved in vasoconstriction and vasodilation system affect salt-sensitive hypertension. PLoS One 6:e19620. doi:10.1371/journal.pone.0019620 CrossRefPubMedPubMedCentral

23.

Lanzani C, Citterio L, Glorioso N, Manunta P, Tripodi G, Salvi E, Carpini SD, Ferrandi M, Messaggio E, Staessen JA, Cusi D, Macciardi F, Argiolas G, Valentini G, Ferrari P, Bianchi G (2010) Adducin- and ouabain-related gene variants predict the antihypertensive activity of rostafuroxin, part 2: clinical studies. Sci Transl Med 2:59ra87. doi:10.1126/scitranslmed.3001814

24.

Lanzani C, Gatti G, Citterio L, Messaggio E, Delli Carpini S, Simonini M, Casamassima N, Zagato L, Brioni E, Hamlyn JM, Manunta P (2016) Lanosterol synthase gene polymorphisms and changes in endogenous ouabain in the response to low sodium intake. Hypertension 67:342–348. doi:10.1161/HYPERTENSIONAHA.115.06415 PubMed

25.

Salvi E, Kutalik Z, Glorioso N, Benaglio P, Frau F et al (2012) Genomewide association study using a high-density single nucleotide polymorphism array and case–control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase. Hypertension 59:248–255. doi:10.1161/HYPERTENSIONAHA.111.181990 CrossRefPubMed

26.

On C, Marshall CR, Chen N, Moyes CD, Tibbits GF (2008) Gene structure evolution of the Na⁺–Ca²⁺ exchanger (NCX) family. BMC Evol Biol 8:127–142. doi:10.1186/1471-2148-8-127 CrossRefPubMedPubMedCentral

27.

Khananshvili D (2013) The SLC8 gene family of sodium–calcium exchangers (NCX)—structure, function, and regulation in health and disease. Mol Aspects Med 34:220–235. doi:10.1016/j.mam.2012.07.003 CrossRefPubMed

28.

Iwamoto T, Kita S, Zhang J, Blaustein MP, Arai Y, Yoshida S, Wakimoto K, Komuro I, Katsuragi T (2004) Salt-sensitive hypertension is triggered by Ca²⁺ entry via Na⁺/Ca²⁺ exchanger type-1 in vascular smooth muscle. Nat Med 10:1193–1199. doi:10.1038/nm1118 CrossRefPubMed

29.

Zhang J, Ren C, Chen L, Navedo MF, Antos LK, Kinsey SP, Iwamoto T, Philipson KD, Kotlikoff MI, Santana LF, Wier WG, Matteson DR, Blaustein MP (2010) Knockout of Na⁺/Ca²⁺ exchanger in smooth muscle attenuates vasoconstriction and L-type Ca2+ channel current and lowers blood pressure. Am J Physiol Heart Circ Physiol 298:H1472–H1483. doi:10.1152/ajpheart.00964.2009 CrossRefPubMedPubMedCentral

30.

Boscia F, Gala R, Pignataro G, de Bartolomeis A, Cicale M, Ambesi-Impiombato A, Di Renzo G, Annunziato L (2006) Permanent focal brain ischemia induces isoform-dependent changes in the pattern of Na⁺/Ca²⁺ exchanger gene expression in the ischemic core, periinfarct area, and intact brain regions. J Cereb Blood Flow Metab 26:502–517. doi:10.1038/sj.jcbfm.9600207 CrossRefPubMed

31.

Pignataro G, Gala R, Cuomo O, Tortiglione A, Giaccio L, Castaldo P, Sirabella R, Matrone C, Canitano A, Amoroso S, Di Renzo G, Annunziato L (2004) Two sodium/calcium exchanger gene products, NCX1 and NCX3, play a major role in the development of permanent focal cerebral ischemia. Stroke 35:2566–2570. doi:10.1161/01.str.0000143730.29964.93 CrossRefPubMed

32.

Staiano RI, Granata F, Secondo A, Petraroli A, Loffredo S, Frattini A, Annunziato L, Marone G, Triggiani M (2009) Expression and function of Na+/Ca2+ exchangers 1 and 3 in human macrophages and monocytes. Eur J Immunol 39:1405–1418. doi:10.1002/eji.200838792 CrossRefPubMed

33.

Popov S, Silveira A, Wågsäter D, Takemori H, Oguro R, Matsumoto S, Sugimoto K, Kamide K, Hirose T, Satoh M et al (2011) Salt-inducible kinase 1 influences Na, K-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure. J Hypertens 29:2395–2403. doi:10.1097/HJH.0b013e32834d3d55 CrossRefPubMed

34.

Stenstrom K, Takemori H, Bianchi G, Katz AI, Bertorello AM (2009) Blocking the salt-inducible kinase 1 network prevents the increases in cell sodium transport caused by a hypertension-linked mutation in human α-adducin. J Hypertens 27:2452–2457. doi:10.1097/HJH.0b013e328330cf15 CrossRefPubMed

35.

Hietakangas V, Cohen SM (2008) TORCing up metabolic control in the brain. Cell Metab 7:357–358. doi:10.1016/j.cmet.2008.04.006 CrossRefPubMed

36.

Hu Z, Hu J, Shen WJ, Kraemer FB, Azhar S (2015) A novel role of Salt-Inducible Kinase 1 (SIK1) in the post-translational regulation of scavenger receptor class B type 1 activity. Biochemistry 54:6917–6930. doi:10.1021/acs.biochem.5b00147 CrossRefPubMed

37.

Degerman E, Rauch U, Göransson O, Lindberg S, Hultgårdh A, Magnusson M (2011) Identification of new signaling components in the sensory epithelium of human saccule. Front Neurol 2:e48. doi:10.3389/fneur.2011.00048 CrossRef

38.

Illarionova NB, Gunnarson E, Li Y, Brismar H, Bondar A, Zelenin S, Aperia A (2010) Functional and molecular interactions between aquaporins and Na, K-ATPase. Neuroscience 168:915–925. doi:10.1016/j.neuroscience.2009.11.062 CrossRefPubMed

39.

Radtke A, Lempert T, Gresty MA, Brookes GB, Bronstein AM, Neuhauser H (2002) Migraine and Ménière’s disease: is there a link? Neurology 59:1700–1704. doi:10.1212/01.wnl.0000036903.22461.39 CrossRefPubMed

40.

Lopez-Escamez JA, Dlugaiczyk J, Jacobs J, Lempert T, Teggi R, von Brevern M, Bisdorff A (2014) Accompanying symptoms overlap during attacks in Menière’s Disease and vestibular migraine. Front Neurol 5:265. doi:10.3389/fneur.2014.00265 CrossRefPubMedPubMedCentral

41.

Lempert T, Olesen J, Furman J, Waterston J, Seemungal B, Carey J, Bisdorff A, Versino M, Evers S, Newman-Toker D (2012) Vestibular migraine: diagnostic criteria. J Vestib Res 22:167–172. doi:10.3233/VES-2012-0453 PubMed

42.

Lang F, Vallon V, Knipper M, Wangemann P (2007) Functional significance of channels and transporters expressed in the inner ear and kidney. Am J Physiol Cell Physiol 293:1187–1208. doi:10.1152/ajpcell.00024.2007 CrossRef

Title: Genetics of ion homeostasis in Ménière’s Disease
Authors: Roberto Teggi
Laura Zagato
Simona Delli Carpini
Lorena Citterio
Claudia Cassandro
Roberto Albera
Wen-Yi Yang
Jan A. Staessen
Mario Bussi
Paolo Manunta
Chiara Lanzani
Publication date: 01-02-2017
Publisher: Springer Berlin Heidelberg
Published in: European Archives of Oto-Rhino-Laryngology / Issue 2/2017
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI: https://doi.org/10.1007/s00405-016-4375-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Genetics of ion homeostasis in Ménière’s Disease

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2017

Histopathological evaluation and long-term results of soft tissue preservation technique in cholesteatoma surgery

A new surgical technique versus an old marker: can expansion sphincter pharyngoplasty reduce C-reactive protein levels in patients with obstructive sleep apnea?

Phonoarticulation in spinocerebellar ataxia type 3

Building 3D anatomical model of coiling of the internal carotid artery derived from CT angiographic data

Congenital cholesteatoma together with ossicular chain anomaly

The adverse impact of surveillance intervals on the sensitivity of FDG-PET/CT for the detection of distant metastases in head and neck cancer patients