Is there an association between T102C polymorphism of the serotonin receptor 2A gene and urinary incontinence?

Abstract

The regulation of bladder function is influenced by central serotonergic modulation. Several genetic polymorphisms related to serotonin control have been described in the literature. T102C polymorphism of the serotonin receptor 2A gene (5-HT2A) has been shown to be associated with certain diseases such as non-fatal acute myocardial infarction, essential hypertension, and alcoholism. In the present study, we examined the association between 5-HT2A gene polymorphism and urinary incontinence in the elderly. A case-control study was performed in 298 elderly community dwellers enrolled in the Gravataí-GENESIS Project, Brazil, which studies gene-environmental interactions in aging and age-related diseases. Clinical, physical, biochemical, and molecular analyses were performed on volunteers. 5-HT2A genotyping was determined by PCR-RFLP techniques using the HpaII restriction enzyme. The subjects had a mean age of 68.05 ± 6.35 years (60-100 years), with 16.9% males and 83.1% females. The C allele frequency was 0.494 and the T allele frequency was 0.506. The CC genotype frequency was 21.78%, the CT genotype frequency was 55.24% and the TT genotype frequency was 22.98%. We found an independent significant association between the TT genotype (35.7%) and urinary incontinence (OR = 2.06, 95%CI = 1.16-3.65). Additionally, urinary incontinence was associated with functional dependence and systolic hypertension. The results suggest a possible genetic influence on urinary incontinence involving the serotonergic pathway. Further investigations including urodynamic evaluation will be performed to better explain our findings.

Association between T102C 5‐HT2A receptor gene polymorphism and 5‐year mortality risk among Brazilian Amazon riparian elderly population

“…Moreover, it is important to point out that, in general, it is difficult to find a robust association and impact of just one SNP on elderly survival. However, in the case of the T102C‐SNP, previous studies performed in different populations indicate alterations in the concentration of HT‐2A receptors and association with chronic diseases and age‐related dysfunctions, that could affect the lifespan (Choi et al, ; Coto et al, ; Fehér et al, ; Jakubczyk et al, ; Lairez et al, ; Noronha et al, ; Prado‐Lima et al, ; Schwanke et al, ; Yamada et al, ).…”

“…An interaction between the T allele of T102C‐SNP and endothelin‐1 variant with hypertension in a Japanese sample was also described by Yamamoto, Jin, & Wu, () as well as an association between the TT genotype and non‐fatal acute myocardial infarction (Yamada et al, ). Other studies have described an association between the TT genotype and nonfatal acute myocardial infarction (Yamada et al, ), urinary incontinence (Noronha et al, ; Schwanke et al, ) or hypertension (Yamamoto et al, ). Irrespective of phenotypes, individuals with the allele T of the polymorphism of the 5HT2A gene showed greater regional brain volumes in the left inferior temporal and left inferior occipital gyri in a study of patients with recent onset schizophrenia, compared to healthy control subjects (Vijayakumari et al, ).…”

“…By contrast, the TT genotype has been associated with some common disorders in elderly subjects such as urinary incontinence (Noronha et al, ; Schwanke et al, ). An interaction between the T allele of T102C‐SNP and endothelin‐1 variant with hypertension in a Japanese sample was also described by Yamamoto, Jin, & Wu, () as well as an association between the TT genotype and non‐fatal acute myocardial infarction (Yamada et al, ).…”

Mechanisms by which the serotonergic system inhibits micturition in rats

“…Administration of dimethyl sulphoxide (DOI), a 5-HT 2A receptor agonist, was reported to increase the electromyographic activity of the external urethral sphincter (Mbaki and Ramage 2008). There is an association between 5-HT 2A polymorphism and stress and/or urge urinary incontinence in elderly human subjects (Schwanke et al 2007). Therefore, 5-HT 2A receptors may have an association with Onuf's nucleus that innervates the external urethral sphincter.…”

910 A systematic review and meta-analysis of candidate gene association studies of lower urinary tract symptoms in men

“…With many studies prioritizing prostate cancer candidate genetic variation for investigation, there was also a significant overrepresentation of genes implicated in the regulation of cell proliferation and apoptosis. Only two studies considered specific LUTS [27,28], with all other studies addressing a composite definition of male LUTS suggestive of BPH. Quantitative syntheses were possible for 35 polymorphisms in or near 24 genes (Table 2).…”