The -1364A/C Aquaporin 5 Gene Promoter Polymorphism Is Not Associated with Menière’s Disease

Objective. Aquaporin 5 plays an important role in maintaining inner ear water and fluid homeostasis. Since the aquaporin (AQP) 5 promoter-1364A/C polymorphism is associated with altered AQP5 expression and this could impact upon key mechanisms of Menière’s disease, we tested the hypothesis that genotypes of the AQP5 promoter-1364A/C polymorphism are associated with the incidences of Menière’s disease (MD), familial Menière’s disease (FMD), or endolymphatic hydrops (EH). Methods. With approval of the local ethics committee, DNA of 102 patients (39 with MD, 54 with FMD, and 9 with EH) and of 292-matched Caucasian controls was isolated from blood samples and genotyped for the AQP 5 promoter-1364A/C polymorphism. The -test was applied to compare genotype distributions and allele frequencies between patients and controls. Results. Overall, genotype frequencies were not different between controls (AA 69%, AC 30%, CC 1%) and patients with MD AA: 65.7% (23 MD, 37 FMD, and 8 EH); AC: 23.5% (12 MD, 11 FMD, and 1 EH); CC: 3.9% (1 MD, 3 FMD, and 0 EH). However, subgroup analysis revealed the CC genotype to be more frequent in patients with FMD (5.9%) than in healthy controls (1%) ( ). Conclusions. Overall, genotypes of the -1364A/C AQP5 gene polymorphism are not associated with a significant increased risk for Menière’s disease. 1. Introduction Although the pathogenesis of Menière’s disease remains unknown it is likely to be multifactorial. One of these factors could be a genetic predisposition. A candidate is the gene encoding aquaporin 5 (AQP5) as aquaporins play an important role in maintaining inner ear fluid homeostasis. Furthermore, AQP5 is preferentially localized within the external sulcus cells and the spiral prominence of the cochlea implying a physiological role of AQP5 in auditory function [1, 2]. Following sequencing of the AQP5 promoter region of 50 healthy white Caucasians we have described a novel, functional, and common single nucleotide (-1364A/C) polymorphism [3]. Substitution of C for A at position -1364 was associated with increased binding of transcription factors, as shown for nuclear extracts from HeLa cells, but reduced transcriptional activation of the AQP5 gene in response to serum and camp [3]. This latter finding is of special interest since stimulation of the vasopressin V2-receptor by arginine-vasopressin (ADH) results in increased AQP5 mRNA concentrations and increased translocation of AQP5 to the plasma membrane [3]. This is mediated via an increase in cAMP concentration and subsequent activation of the protein kinase A pathway.