Polymorphism Of Scn9a Gene Is More Frequent In Bladder Pain Syndrome /Interstitial Cystitis Biopsy Specimens And Associated With Higher Pain Scores

RD Mayer1, JE Reeder2. 1University of Rochester, Urology 14642, USA, 2SUNY Upstate Medical University, Urology 13210, USA

Objective: Bladder pain syndrome/Interstitial cystitis (BPS/IC) is an idiopathic visceral hypersensitivity syndrome characterized by pelvic/bladder pain, urgency and frequency. There is no known cure and available therapies are only modestly effective. Improved therapy for these patients will likely depend on defining subgroups allowing more selective interventions. Polymorphisms / mutations in the voltage gated sodium channel NaV1.7 encoded by the SCN9A gene are found at increased frequency for several chronic pain syndromes. In patients with similar physical findings variability in reported pain was associated with the A allele in SNP rs6746030 (Reimann 2010). The A allele is present in approximately ten percent of the CEU population and results in a missense mutation at amino acid 1150 changing an arginine codon to a trytophan codon (R1150W). The objective of the study was to determine genotype frequencies at this candidate SNP in archival BPS/IC biopsy tissue and the relationship of these genotypes to reported pain.

Methods: Archived tissue of bladder biopsy specimens from 27 patients with a documented diagnosis of IC was obtained under an approved institutional IRB protocol compared to a control population of 26 archived hysterectomy specimens. Chart review determined gender, pain score and presence of bladder ulcers. Genotyping was done blinded to clinical characteristics. SNP genotyping was performed by allele specific amplification for the rs6746030 SNP validated by DNA sequencing. SPSS statistical program was utilized to analyze the results.

Results: Twenty of 27 IC/PBS patients were female, 17 had no ulcers and 10 had ulcers, 10 of 27 had AG genotype, 2 specimens failed to yield adequate DNA and 15 had GG genotype to yield a 40% incidence of AG genotype in comparison to 3 of 26 (11.5%) in the control population and 10% reported in the general population. No AA genotypes were detected in either the IC/PBS or control populations. There was no significant difference in percentage of patients with AG depending on presence or absence of ulcers. The mean pain scores of patients with AG was 5.8 (SD 2.8) compared to 3.4 (SD 2.9) for GG genotype, p< 0.05. There was no significant difference in pain scores between those with and without ulcers, mean 3.4 vs 4.8 respectively.

Conclusions: The frequency of AG polymorphism for SCN9A in this retrospective sample of IC patients is four times higher than expected suggesting that this abnormality may play a role in a significant number of patients with this syndrome, and also possibly predict patients with higher pain severity.