Pottery from the interstage of Neolithic and Bronze Age and from later epochs

<div><p>Meniere's disease is an episodic vestibular syndrome associated with sensorineural hearing loss (SNHL) and tinnitus. Patients with MD have an elevated prevalence of several autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and psoriasis), which suggests a shared autoimmune background. Functional variants of several genes involved in the NF-κB pathway, such as <i>REL</i>, <i>TNFAIP3</i>, <i>NFKB1</i> and <i>TNIP1</i>, have been associated with two or more immune-mediated diseases and allelic variations in the <i>TLR10</i> gene may influence bilateral affectation and clinical course in MD. We have genotyped 716 cases of MD and 1628 controls by using the ImmunoChip, a high-density genotyping array containing 186 autoimmune loci, to explore the association of immune system related-loci with sporadic MD. Although no single nucleotide polymorphism (SNP) reached a genome-wide significant association (p<10⁻⁸), we selected allelic variants in the NF-kB pathway for further analyses to evaluate the impact of these SNPs in the clinical outcome of MD in our cohort. None of the selected SNPs increased susceptibility for MD in patients with uni or bilateral SNHL. However, two potential regulatory variants in the <i>NFKB1</i> gene (rs3774937 and rs4648011) were associated with a faster hearing loss progression in patients with unilateral SNHL. So, individuals with unilateral MD carrying the C allele in rs3774937 or G allele in rs4648011 had a shorter mean time to reach hearing stage 3 (>40 dB HL) (log-rank test, corrected p values were p = 0.009 for rs3774937 and p = 0.003 for rs4648011, respectively). No variants influenced hearing in bilateral MD. Our data support that the allelic variants rs3774937 and rs4648011 can modify hearing outcome in patients with MD and unilateral SNHL.</p></div

Linkage disequilibrium plot showing the haploblocks with the rs3774937 and rs4648011 (r² = 0.67, D' = 0.95).

<p>Linkage disequilibrium plot showing the haploblocks with the rs3774937 and rs4648011 (r² = 0.67, D' = 0.95).</p

Single nucleotide polymorphisms in the NF-κB pathway with reported associations.

a<p>NCBI human genome build 37 coordinates.</p>b<p>http://<a href="http://www.ncbi.nlm.nih.gov/gap" target="_blank">www.ncbi.nlm.nih.gov/gap</a><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0112171#pone.0112171-Tryka1" target="_blank">[38]</a>.</p><p>Single nucleotide polymorphisms in the NF-κB pathway with reported associations.</p

Effect of allelic variants in the NF-κB pathway on hearing loss progression in patients with Meniere's disease.

<p>Mean time to reach stage 3 (>40 dB) was compared by Kaplan –Meier survival curves and long-rank test.</p><p>*corrected p values after Bonferroni's method.</p><p>Effect of allelic variants in the NF-κB pathway on hearing loss progression in patients with Meniere's disease.</p

Clinical features of patients with Meniere's disease and uni or bilateral sensorineural hearing loss.

<p><b>Age of onset, time course years and hearing loss at diagnosis were compared by unpaired Student's t test. Qualitative variables were compared by Chi-squared test.</b></p><p>Clinical features of patients with Meniere's disease and uni or bilateral sensorineural hearing loss.</p