The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder

Dis Markers. 2015:2015:732686. doi: 10.1155/2015/732686. Epub 2015 Jun 24.

Abstract

Aim: To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS).

Materials and methods: Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method.

Results: 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes.

Conclusions: The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Cholinergic Antagonists / therapeutic use*
  • Cytochrome P-450 CYP3A / genetics
  • Female
  • Humans
  • Male
  • Mandelic Acids / therapeutic use*
  • Polymorphism, Restriction Fragment Length*
  • Receptors, Adrenergic, beta-3 / genetics
  • Rho Guanine Nucleotide Exchange Factors / genetics
  • Treatment Outcome
  • Urinary Bladder, Overactive / drug therapy*
  • Urinary Bladder, Overactive / genetics
  • rho-Associated Kinases / genetics

Substances

  • ADRB3 protein, human
  • ARHGEF10 protein, human
  • Cholinergic Antagonists
  • Mandelic Acids
  • Receptors, Adrenergic, beta-3
  • Rho Guanine Nucleotide Exchange Factors
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • ROCK2 protein, human
  • rho-Associated Kinases
  • oxybutynin