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.
journal_name
DNA Cell Bioljournal_title
DNA and cell biologyauthors
Gazquez I,Lopez-Escamez JA,Moreno A,Campbell CA,Meyer NC,Carey JP,Minor LB,Gantz BJ,Hansen MR,Della Santina CC,Aran I,Soto-Varela A,Santos S,Batuecas A,Perez-Garrigues H,Lopez-Nevot A,Smith RJ,Lopez-Nevot MAdoi
10.1089/dna.2011.1259subject
Has Abstractpub_date
2011-09-01 00:00:00pages
699-708issue
9eissn
1044-5498issn
1557-7430journal_volume
30pub_type
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