title: Functional variants in NOS1 and NOS2A are not associated with progressive hearing loss in Ménière's disease in a European Caucasian population.
abstract: Hearing loss in Ménière'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, we 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 NOS2A do not confer susceptibility for MD.
authors: Otology and Neurotology Group CTS495, GENYO, Centro de Genómica e Investigación Oncológica-Pfizer, Universidad de Granada, Junta de Andalucía, Granada, Spain.
authors: Irene
authors: I
authors: Gazquez
authors: Jose A
authors: JA
authors: Lopez-Escamez
authors: Antonia
authors: A
authors: Moreno
authors: Colleen A
authors: CA
authors: Campbell
authors: Nicole C
authors: NC
authors: Meyer
authors: John P
authors: JP
authors: Carey
authors: Lloyd B
authors: LB
authors: Minor
authors: Bruce J
authors: BJ
authors: Gantz
authors: Marlan R
authors: MR
authors: Hansen
authors: Charles C
authors: CC
authors: Della Santina
authors: Ismael
authors: I
authors: Aran
authors: Andres
authors: A
authors: Soto-Varela
authors: Sofia
authors: S
authors: Santos
authors: Angel
authors: A
authors: Batuecas
authors: Herminio
authors: H
authors: Perez-Garrigues
authors: Alicia
authors: A
authors: Lopez-Nevot
authors: Richard J H
authors: RJ
authors: Smith
authors: Miguel A
authors: MA
authors: Lopez-Nevot