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A genome‐scale DNA methylation study in women with interstitial cystitis/bladder pain syndrome
Author(s) -
Bradley Megan S.,
Burke Emily E.,
Grenier Carole,
Amundsen Cindy L.,
Murphy Susan K.,
Siddiqui Nazema Y.
Publication year - 2018
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.23489
Subject(s) - dna methylation , cpg site , medicine , methylation , interstitial cystitis , urine , interquartile range , biomarker , genotype , gene , urinary system , genetics , gene expression , biology
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 Sixteen participants (eight IC/BPS age‐ and race‐matched to eight 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.

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