Association analysis of ADRB3:rs4994 with urodynamic outcome, six months after a single intra-detrusor injection of botulinum toxin, in women with overactive bladder

Pharmacol Rep. 2024 Dec;76(6):1489-1500. doi: 10.1007/s43440-024-00647-9. Epub 2024 Sep 11.

Abstract

Background: Intra-detrusor injection of botulinum neurotoxin type A (BoNT/A) is recommended as a possible treatment for patients with overactive bladder (OAB) in whom first-line therapies have failed. The c.190T > C (rs4994) polymorphism in the gene encoding the beta-3 adrenergic receptor (ADRB3) has been suggested to be associated with predisposition to OAB or with response to OAB treatment via a cholinergic muscarinic receptor antagonist. This prospective study aimed to use a urodynamic parameter-based assessment of response, six months after a single intra-detrusor injection of BoNT/A in female OAB patients, to elucidate possible association with the ADRB3 polymorphism.

Methods: The study group consisted of 138 consecutive, Polish, adult, female OAB patients. Urodynamic parameters were recorded before injection of BoNT/A and at six months after administration. ADRB3:rs4994 variants were identified by the sequencing of genomic DNA extracted from buccal swabs.

Results: Apart from baseline, and relative, increase in Maximum Cystometric Capacity (MCC) six months after BoNT/A injection, no significant differences were found in urodynamic parameters between reference TT homozygotes and women with at least one C allele.

Conclusions: Our results do not exclude that ADRB3:rs4994 variants are associated with a positive urodynamic test-based response to intra-detrusor injection of BoNT/A in females with OAB.

Keywords: Beta-3 adrenoreceptor; Botulinum neurotoxin-A; Gene polymorphism; Overactive bladder, urodynamic assessment.

MeSH terms

  • Adult
  • Aged
  • Botulinum Toxins, Type A* / administration & dosage
  • Female
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Receptors, Adrenergic, beta-3* / genetics
  • Treatment Outcome
  • Urinary Bladder, Overactive* / drug therapy
  • Urinary Bladder, Overactive* / genetics
  • Urinary Bladder, Overactive* / physiopathology
  • Urodynamics* / drug effects

Substances

  • Botulinum Toxins, Type A
  • Receptors, Adrenergic, beta-3
  • ADRB3 protein, human