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The following is a summary of “Association of COMT genetic polymorphism with neuromodulation treatment response in women with fecal or urinary incontinence,” published in the March 2025 issue of American Journal of Obstetrics & Gynecology by Florian-Rodriguez et al. 

Previous studies showed no significant difference in fecal incontinence (FI) improvement between PTNS and sham treatments, suggesting a possible placebo effect.  

Researchers conducted a retrospective study to examine genetic biomarkers associated with placebo response in women receiving percutaneous tibial nerve stimulation (PTNS) for FI.  

They examined the blood specimens from 96 women in the Neuromodulation for Accidental Bowel Leakage trial who provided consent for future research. DNA extraction and genotyping targeted single nucleotide polymorphisms (SNPs) in genes linked to placebo response, including catechol-O-methyltransferase (COMT), tryptophan hydroxylase-2 (TPH2), brain-derived neurotrophic factor (BDNF), fatty acid amide hydrolase (FAAH), and mu-opioid receptors (OPRM1). An additive linear regression interaction model, adjusted for BMI, race, baseline fecal incontinence episodes (FIEs), or St. Mark’s score, assessed SNP-by-treatment interactions associated with St. Mark’s score changes after 12 weeks. If no significant interaction was found, SNP main effects were tested. Findings were validated using an independent cohort from a randomized trial on urgency urinary incontinence, comparing sacral neuromodulation (SNM) and onabotulinumtoxinA.  

The results showed no differences in age, BMI, FIEs, or St. Mark’s score at baseline or follow-up between PTNS participants (n=64) and sham participants (n=32). A significant interaction (P <0.1) was found between the COMT SNP and treatment for St. Mark’s score improvement (P =0.02), FIE reduction (P =0.01), and Patient Global Impression of Improvement (PGI-I) (P =0.06) and PTNS participants with the COMT Met allele showed the greatest improvement, with a St. Mark’s score decrease of 1.72 (95% CI=[-0.04 – 3.49], P =0.06), a reduction of 2.36 FIEs per week (95% CI=[0.97-3.75], P =0.001), and a PGI-I OR of 2.00 (95% CI=[0.96-4.14], P =0.06). No association between COMT and treatment response was observed in the sham group. Other SNPs showed no significant interactions or main effects. In an independent urinary incontinence study, the Met allele was significantly associated with PGI-I urinary leak improvement (OR 2.41, 95% CI=[1.27-4.55], P =0.007) and PGI-I bladder function improvement (OR 2.10, 95% CI=[1.10-4.01], P=0.03) in women treated with SNM, but no association was found in the onabotulinumtoxinA group.  

Investigators concluded that women homozygous for the COMT Met allele demonstrated a significantly higher response to neuromodulation treatments for fecal and urinary incontinence but not to sham treatments. 

Source: ajog.org/article/S0002-9378(25)00152-8/abstract