Role of β‐3 adrenergic receptor polymorphism in overactive bladder

Abstract

Aims Women with overactive bladder (OAB) have a higher frequency of a single‐nucleotide polymorphism (SNP) at codon 64 of the β‐3 adrenergic receptor gene (ADRB3). Since the SNP results in an amino acid substitution that could theoretically alter receptor protein function, we hypothesized that those with the SNP would display greater OAB symptom severity. Therefore we aimed to compare OAB severity between women with this SNP and women with the wild type genotype. Methods A retrospective cohort study was performed in women with bothersome OAB from two academic institutions. Banked blood samples were tested for the codon 64 SNP. Women were divided into two groups based on genotype: wild‐type (WT) and heterozygous (HZ). We compared mean OAB Symptom Severity questionnaire (OAB‐q) scores between groups using t tests. Linear regression was performed to control for potential confounders. Results Of the 303 women with OAB, 254 (83.8%) had the WT genotype, and 49 (16.2%) the HZ genotype. There were no homozygous women for the rare allele. The majority were Caucasian (86%) and non‐Hispanic (97%). There were no significant differences in mean OAB‐q symptom severity scores (WT 21.2 ± 7 vs HZ 22.0 ± 6.6; P = 0.49) and quality of life scores (WT 39.6 ± 15.5 vs HZ 39.1 ± 16.6; P = 0.83) between groups. These remained nonsignificant in a linear regression model. Conclusions In a predominantly non‐Hispanic, Caucasian population of women with bothersome OAB, symptom severity was not related to ADRB3 codon 64 SNP genotype.

Association between the Trp64Arg polymorphism of the ADRB3 gene and overactive bladder

“…26 In another newly published study, 303 women (predominantly non-Hispanic, Caucasian population) with OAB were investigated for the Trp64Arg polymorphism, 83.8% were found as wild-type and 16.2% heterozygous. 27 That means that the wild-type (T) and variant allele (C) of Trp64Arg polymorphism frequency was 91.9% and 8.1%, respectively. No relationship was found In the present study, we compared the frequency distribution of Trp64Arg polymorphism in OAB patients and non-OAB controls.…”

“…Another recently published study showed also that ADRB3 polymorphism is not associated with the clinic of OAB patients of Turkish ancestry 26 . In another newly published study, 303 women (predominantly non‐Hispanic, Caucasian population) with OAB were investigated for the Trp64Arg polymorphism, 83.8% were found as wild‐type and 16.2% heterozygous 27 . That means that the wild‐type (T) and variant allele (C) of Trp64Arg polymorphism frequency was 91.9% and 8.1%, respectively.…”

Association Between Trp64Arg Polymorphism of Beta-3 Adrenergic Receptor Gene and Susceptibility to Overactive Bladder: A Meta-Analysis

“…Although several factors seem to be involved in the mechanisms underlying OAB, present studies may suggest that dysfunction of beta3-AR resulting from its gene polymorphism, at least partially, conduces to the pathophysiology underlying OAB ( Yamaguchi, 2002 ; Yamaguchi and Chapple, 2007 ; Peyronnet et al, 2019 ). Therefore, Trp64Arg polymorphism of ADRB3 , leading to a missense mutation and altering receptor function, would be speculated on increased susceptibility to OAB ( Ferreira et al, 2011 ; Meekins et al, 2019 ).…”

“…Previous studies of families and twins have suggested a genetic predisposition to OAB ( Rohr et al, 2004 ; Wennberg et al, 2011 ). Trp64Arg polymorphism (ID rs4994) of ADRB3 leads to a missense mutation resulting in an amino acid change from tryptophan to arginine and altering receptor function, which has been proposed as a pathophysiologic mechanism for OAB ( Michel and Korstanje, 2016 ; Meekins et al, 2019 ).…”

“…There are only a few original studies on the relationship between Trp64Arg polymorphism and OAB; moreover, the results are contradictory and available evidence remains limited ( Yamaguchi, 2002 ; Ferreira et al, 2011 ; Teitsma et al, 2013 ; Honda et al, 2014 ; Gurocak et al, 2015 ; Meekins et al, 2019 ; Fırat et al, 2020 ; Çırakoğlu et al, 2021 ). In order to overcome the limitations of individual study and acquire a more accurate estimation of the association between Trp64Arg polymorphism and susceptibility to OAB, this meta-analysis was performed.…”