Functional Variants in NOS1 and NOS2A Are Not Associated with Progressive Hearing Loss in Ménière's Disease in a European Caucasian Population


Autoria(s): Gazquez, Irene; Lopez-Escamez, Jose A.; Moreno, Antonia; Campbell, Colleen A.; Meyer, Nicole C.; Carey, John P.; Minor, Lloyd B.; Gantz, Bruce J.; Hansen, Marlan R.; Della Santina, Charles C.; Aran, Ismael; Soto-Varela, Andres; Santos, Sofia; Batuecas, Angel; Perez-Garrigues, Herminio; Lopez-Nevot, Alicia; Smith, Richard J.H.; Lopez-Nevot, Miguel A.
Data(s)

12/06/2012

12/06/2012

09/09/2011

Resumo

Hearing loss in Meniere's disease (MD) is associated with loss of spiral ganglion neurons and hair cells. In a guinea pig model of endolymphatic hydrops, nitric oxide synthases (NOS) and oxidative stress mediate loss of spiral ganglion neurons. To test the hypothesis that functional variants of NOS1 and NOS2A are associated with MD, wed genotyped three functional variants of NOS1 (rs41279104,rs2682826, and a cytosine-adenosine microsatellite repeat in exon 1f) and the CCTTT repeat in the promoter of NOS2A gene (rs3833912) in two independent MD sets(273 patients in total) and 550 controls. A third cohort of American patients was genotyped as replication cohort for the CCTTT repeat. Neither allele nor genotype frequencies of rs41279104 and rs2682826 were associated with MD, although longer alleles of the cytosine-adenosine microsatellite repeat were marginally significant (corrected p = 0.05) in the Mediterranean cohort but not in a second Galicia cohort. Shorter numbers of the CCTTT repeat in NOS2A were significantly more frequent in Galicia controls (OR = 0.37 [CI, 0.18-0.76], corrected p =0.04), but this finding could not be replicated in Mediterranean or American case-control populations. Meta-analysis did not support an association between CCTTT repeats and risk for MD. Severe hearing loss (>75 dB) was also not associated with any functional variants studied. Functional variants of NOS1 and and NOS2A do not confer susceptibility for MD.

This is a copy of an article published in the DNA and Cell Biology © 2011 [copyright Mary Ann Liebert, Inc.]; DNA and Cell Biology is available online at: http://online.liebertpub.com.

This study was funded by an FIS PI10/0920 Research Project from ISCIII. J.A.L.-E. was partially supported by ISCIII research grant INT09/229. The 3130 XL Genetics Analyzer was funded by grant IF06/37291 from Ministry of Science. This work was partially supported by the University of Iowa, Department of Otolaryngology and the Research Fund of the American Otological Society (to R.J.H.S.).

Identificador

Gazquez I, Lopez-Escamez JA, Moreno A, Campbell CA, Meyer NC, Carey JP, et al. Functional Variants in NOS1 and NOS2A Are Not Associated with Progressive Hearing Loss in Ménière's Disease in a European Caucasian Population. DNA Cell Biol. 2011 Sep;30(9):699-708

1557-7430 (Online)

1044-5498 (Print)

http://hdl.handle.net/10668/408

21612410

10.1089/dna.2011.1259.

Idioma(s)

en

Publicador

Mary Ann Liebert

Relação

DNA and Cell Biology

http://online.liebertpub.com/doi/abs/10.1089/dna.2011.1259

Direitos

Acceso restringido

Palavras-Chave #Secuencia de Bases #Sitios de Unión #Grupo de Ascendencia Continental Europea #Frecuencia de los Genes #Variación Genética #Genotipo #Pérdida Auditiva #Humanos #Enfermedad de Meniere #Repeticiones de Microsatélite #Datos de Secuencia Molecular #Óxido Nítrico Sintasa de Tipo I #Regiones Promotoras Genéticas #Análisis de Secuencia #España #Estados Unidos #Óxido Nítrico Sintasa de Tipo I #Medical Subject Headings::Information Science::Information Science::Information Services::Documentation::Molecular Sequence Data::Base Sequence #Medical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Binding Sites #Medical Subject Headings::Named Groups::Persons::Population Groups::Continental Population Groups::European Continental Ancestry Group #Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Gene Frequency #Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation #Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype #Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Neurologic Manifestations::Sensation Disorders::Hearing Disorders::Hearing Loss::Hearing Loss, Sensorineural #Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans #Medical Subject Headings::Diseases::Otorhinolaryngologic Diseases::Ear Diseases::Labyrinth Diseases::Endolymphatic Hydrops::Meniere Disease #Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Tandem Repeat Sequences::Microsatellite Repeats #Medical Subject Headings::Information Science::Information Science::Information Services::Documentation::Molecular Sequence Data #Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-NH2 Group Donors::Amino Acid Oxidoreductases::Nitric Oxide Synthase::Nitric Oxide Synthase Type I #Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on CH-NH2 Group Donors::Amino Acid Oxidoreductases::Nitric Oxide Synthase::Nitric Oxide Synthase Type II #Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Gene Components::Regulatory Elements, Transcriptional::Promoter Regions, Genetic #Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA #Medical Subject Headings::Geographicals::Geographic Locations::Europe::Spain #Medical Subject Headings::Geographicals::Geographic Locations::Americas::North America::United States
Tipo

info:eu-repo/semantics/article

info:eu-repo/semantics/published

Artículo