A genome‐scale DNA methylation study in women with interstitial cystitis/bladder pain syndrome

Abstract

Aims To assess the feasibility of using voided urine samples to perform a DNA methylation study in females with interstitial cystitis/bladder pain syndrome (IC/BPS) as compared to age- and race-matched controls. A unique methylation profile could lead to a non-invasive, reproducible, and objective biomarker that would aid clinicians in the diagnosis of IC/BPS. Methods Nineteen IC/BPS patients and 17 controls were included. IC/BPS patients had an Interstitial Cystitis Symptom Index score of >8; controls had no bladder symptoms. DNA was extracted from pelleted urine sediment. Samples with >500 ng of genomic DNA underwent quantitative DNA methylation assessment using the Illumina Infinium MethylationEPIC BeadChip. Age- and race- matching was applied prior to analysis. Linear regression models were used to compare average methylation between IC/BPS cases and controls at each cytosine guanine dinucleotide site (loci where methylation can occur). Results 16 participants (8 IC/BPS age- and race-matched to 8 controls) had adequate DNA for methylation analysis. The median age was 43.5 years (interquartile range 33.8, 65.0), the median BMI was 27.1 (IQR 22.7, 31.4), and 14 were Caucasian (87.5%). A total of 688,417 CpG sites were analyzed. In exploratory pathway analysis utilizing the top 1000 differentially methylated CpG sites, the mitogen-activated protein kinase (MAPK) pathway was overrepresented by member genes. Conclusions The results demonstrate the feasibility of using voided urine specimens from women with IC/BPS to perform DNA methylation assessments. Additionally, the data suggest genes within or downstream of the MAPK pathway exhibit altered methylation in IC/BPS.

Targeting epigenetic mechanisms for chronic visceral pain: A valid approach for the development of novel therapeutics

“…These affected genes were associated with the glutathione metabolism related to oxidative stress and neuropeptide hormone activity . A genomewide methylation study on voided urine from patients with interstitial cystitis revealed genes downstream of the MAPK pathways were differentially methylated when compared to healthy controls . These studies highlight the epigenetic changes in the target tissues of patients.…”

“…123 A genomewide methylation study on voided urine from patients with interstitial cystitis revealed genes downstream of the MAPK pathways were differentially methylated when compared to healthy controls. 124…”

Inhibition of U‐II/UT signaling ameliorates cystitis‐associated bladder hyperactivity by targeting the RhoA/Rho‐kinase pathway

“…The symptom of frequency or urgency is far more common than that of bladder discomfort 2 . The overall prevalence range of IC/BPS is approximately 2.7%–6.5%, and this disease can cause massive financial costs and severely impair the health‐related quality of life 3 . In addition, IC/BPS is more prevalent in women with an estimated female‐to‐male ratio ranging from 5:1 to 10:1 4 .…”

“…2 The overall prevalence range of IC/BPS is approximately 2.7%-6.5%, and this disease can cause massive financial costs and severely impair the health-related quality of life. 3 In addition, IC/BPS is more prevalent in women with an estimated female-to-male ratio ranging from 5:1 to 10:1. 4 To date, the pathophysiology of IC/BPS is still not fully understood and no optimal treatment for this disease has been established.…”

Adenosine A2A Receptor Agonist Polydeoxyribonucleotide Alleviates Interstitial Cystitis-Induced Voiding Dysfunction by Suppressing Inflammation and Apoptosis in Rats

“… 8 MAPK is associated with inhibition of cell growth, inflammation, and with mediating apoptosis in different cell types. 9 MAPK and NF-κB are phosphorylated and then activated by many stimuli such as cytokines and cell stress. 10 Activation of MAPK/NF-κB can promote the expression of various pro-inflammatory cytokines, thereby regulating inflammation and apoptosis.…”