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Association Between T102C Polymorphism of Serotonin 2A Receptor Gene and Urinary Incontinence in Older Women
  1. Jorge Antônio Pastro Noronha, PhD, MD*,
  2. Carla Helena Augustin Schwanke, MD, PhD,
  3. Denise Cantarelli Machado, PhD,
  4. Rafael Braga, MD§,
  5. Jeremia Mistrello Lubianca, MD,
  6. Fabiane Lorenzoni Sesti, MD,
  7. Aloysio Floriano de Toledo, PhD*,
  8. Ivana Beatrice Mânica da Cruz, PhD**
  1. From the *Serviço de Urologia, Hospital São Lucas and Faculdade de Medicina, †Instituto de Geriatria e Gerontologia, Programa de Pós-Graduação em Gerontologia Biomédica, ‡Faculdade de Medicina, Programa de Pós-Graduação em Medicina e Ciências da Saúde, §Faculdade de Medicina, and∥Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul; ¶Hospital Dom Vicente Scherer da Santa Casa de Misericórdia de Porto Alegre; and **Centro de Ciências da Saúde, Programa de Pós-Graduação em Bioquímica Toxicológica, Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Porto Alegre, Brazil.
  1. Received June 30, 2009, and in revised form August 30, 2009.
  2. Accepted for publication September 3, 2009.
  3. Reprints: Ivana Beatrice Mânica da Cruz, PhD, Av Ipiranga, 6690-601, Porto Alegre, RS, Brazil 90610-000. E-mail: ibmcruz{at}hotmail.com.
  4. Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil (Nos. 471233/2007-2 and 311231/2006-3), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil (No. 266/08), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS).

Abstract

Background The bladder's regulatory function is influenced by central serotonergic modulation. T102C polymorphism of the serotonin 2A (5-HT2A) receptor gene is associated with urinary incontinence (UI) that has been reported by older community dwellers. We analyzed the association between 5-HT2A receptor gene polymorphism and urodynamic tests for UI in older women.

Methods A case-control study was performed with 68 older women submitted to urodynamic evaluation and 162 older women without urinary problems (self-reported), all community dwellers enrolled in the Gravataí-GENESIS Project, Brazil. Clinical interviews, complete urodynamic evaluation following the International Continence Society Report on Good Urodynamic Practice (case group), and molecular analyses were performed (case and control groups). Serotonin 2A receptor gene genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism using the restriction enzyme HpaII. We excluded patients with diabetes mellitus, neurologic damage, and diuretic intake.

Results The subjects' mean (SD) age was 68.1 (6.5) years (range, 60-92 years). We found an association between the TT genotype versus CC + CT genotypes and UI (P = 0.013; odds ratio, 2.69; 95% confidence interval, 1.37-5.29) and, in addition, an association with urgency UI, maximal cystometric capacity (TT, 349 mL; CC + CT, 429.5 mL [P = 0.047]), detrusor pressure at maximum cystometric capacity (TT, 11 cm H2O; CC + CT, 6.75 cm H2O [P = 0.032]), and detrusor compliance (TT, 34 mL/cm H2O; CC + CT, 61.25 mL/cm H2O [P = 0.006]).

Conclusions We confirmed our previous findings of a genetic influence of the TT genotype on UI involving the serotonergic pathway among older women. Further investigations including 5-HT2A expression in the bladder, pelvic floor, and striated sphincter muscle must be performed.

Key Words
  • serotonin 2A receptor
  • 5-HT2A receptor
  • serotonin
  • genetic polymorphism
  • T102C polymorphism of the serotonin 2A receptor gene
  • 5-HT2A gene polymorphism
  • urinary incontinence
  • urgency urinary incontinence
  • urodynamics
  • aged
  • female
  • older women

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