Introduction and aim of the study: Endothelin is a potent constrictor of smooth muscle. Both endothelin A (EDRA) and endothelin B (EDRB) receptors are widely distributed in human bladder. A recent genome-wide association study identified a risk locus for urgency incontinence close to the endothelin 1 gene (EDN1). The aim of the study was to explore the role of endothelin in overactive bladder (OAB).
Materials and methods: Paired urine and blood samples were collected from 263 women. Genotyping for the rs34998271 single nucleotide polymorphism close to the EDN1 gene was performed using specific PCR. Urinary endothelin was tested using the ELISA kit. Bladder biopsies were collected directly into ice cold RNAlater.
Results: Urinary endothelin was present at a mean of 1.13 pg/ml. Urinary endothelin concentrations were significantly associated with OAB severity. The rs34998271 SNP was successfully typed for participants who provided DNA. The minor allele frequency was 4.29% (HWE p > 0.05), consistent with data from the 1000 Genomes project (5.1%). We found that the endothelin type A receptor (EDNRA) was more strongly expressed than type B (EDNRB) in bladder. There was statistically significant differential expression (OAB vs. controls), for 7 of 19 genes within the endothelin pathway.
Interpretation of results: We found that endothelin was expressed in human urine, with significantly less endothelin present for women with OAB. At least using these random midstream urine samples, the effect size was small, suggesting that endothelin is unlilkely to be a clinically useful biomarker for OAB. We found strong evidence for differential expression of genes in the endothelin pathway in OAB, suggesting the possibility of multiple drug targets.
Conclusions: Endothelin is significantly underexpressed in urine for women with OAB. Multiple genes within the endothelin pathway are differentially expressed in association with OAB, suggesting therapeutic potential for drugs that act in this pathway.
© 2017 Published by Elsevier Inc.