Aquaporin-2 and -4: Single nucleotide polymorphisms in Ménière's disease patients

Abstract The endolymphatic hydrops seen in Ménière's disease (MD) results from an inner ear fluid disequilibrium that has a suspected inherited component. Aquaporin-2 and aquaporin-4 (AQP2 and AQP4) water transport proteins may contribute to abnormal fluid homeostasis seen in MD. Our objective was to screen for sequence alterations in AQP2 and AQP4 genes in a northern European population with MD. Amplification for AQP2 (n = 18) and AQP4 (n = 30) was performed for patients with MD. Sequences were screened with denaturing high powered liquid chromatography (DHPLC) and confirmed with sequencing. Allele frequencies were compared with previously reported normal populations. We found that DHPLC failed to identify sequence alterations in any sample. Sequencing identified three intronic and one 3’ untranslated region polymorphism in AQP2, and one polymorphism upstream from the start codon in AQP4. Two of the AQP2 intronic allele frequencies showed an A and C allele enrichment, respectively, compared with a reported mixed population (0.389 A vs. 0.00 A; 0.389 C vs. 0.00 C, p<0.001). The remaining polymorphism showed statistical difference from three non-Caucasian populations (0.611 A vs. 0.389 A, 0.375 A, and 0.280 A, p<0.05). The AQP4 allele frequency in the MD population was statistically different from a previously published Japanese population (0.800 G vs. 0.620 G, p = 0.0053) but not from a reported Caucasian population. We concluded that aquaporin polymorphisms may contribute to MD. Additional studies are needed to confirm these findings in well-defined population isolates and to determine if these polymorphisms lead to altered AQP protein function or levels.