title: Genetics of ion homeostasis in Ménière's Disease.
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.
authors.affiliation: ENT Division, Department of ENT, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy. teggi.roberto@hsr.it.
authors.forename: Roberto
authors.identifier: http://orcid.org/0000-0003-2948-4638
authors.initials: R
authors.lastname: Teggi
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics and Cellular Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Zagato
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics and Cellular Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Delli Carpini
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics and Cellular Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Citterio
authors.affiliation: Surgical Sciences Department, University of Turin, Turin, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cassandro
authors.affiliation: Surgical Sciences Department, University of Turin, Turin, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Albera
authors.affiliation: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Louvain, Belgium.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Yang
authors.affiliation: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Louvain, Belgium.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Staessen
authors.affiliation: ENT Division, Department of ENT, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Bussi
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics and Cellular Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Chair of Nephrology, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Manunta
authors.affiliation: Genomics of Renal Diseases and Hypertension Unit, Division of Genetics and Cellular Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.|Chair of Nephrology, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Lanzani
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D007477:Ions / Q000378:metabolism*; D008297:Male; D008575:Meniere Disease / Q000150:complications / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014717:Vertigo / Q000150:complications; D044465:White People / Q000235:genetics*
chemical_list: D007477:Ions
keywords: Genetics; Ionic transporters; Ménière’s Disease; Na+-Ca++ exchanger 1 (SLC8A1); Salt inducible kinase 1 (SIK1)