Epigenetic differences in non-plaque tissues of men with Peyronie's disease.

Abstract

Background: Peyronie's disease (PD) is a fibrosing disorder with a hereditary predisposition that can have significant impacts on quality of life.

Aim: Our pilot study's objective was to determine if disease penetrance is correlated with epigenetic variations in non-plaque tissue, as compared with tissue from men with erectile dysfunction (ED), as indicated by DNA methylation.

Methods: Tunica albuginea samples were collected from non-plaque tissue during penile prosthesis placement for men with ED with and without PD, with ED-only samples serving as controls. DNA methylation analyses were performed on homogenized penile tissue samples via an Illumina Human MethylationEPIC BeadChip v2 array. Using the minfi package in R, beta values were produced for all 936 990 CpG sites for each sample and subset-quantile within array normalization (SWAN) normalization was applied. Differentially methylated regions (DMRs) were found via USeq with a threshold Wilcoxon FDR score of 40.

Outcomes: The primary outcome of the study was the prevalence and significance of DMRs between samples and controls.

Results: A total of 10 ED + PD and 12 ED-only samples were successfully processed for subsequent epigenetic analyses. Thirty-six DMRs with 60 total region-gene associations and five implicated biological processes were identified, including anterior/posterior pattern specification, chordate embryonic development, embryo development (ending in birth or egg hatching), somitogenesis, and pattern specification process. Each of the implicated biological processes are essential components of the human body's developmental biology and the specific region-gene associations suggest pathogenesis may be an early embryonic development.

Clinical implications: The identification of these epigenetic changes in non-plaque tissue suggests a systemic process related to PD that is not isolated to plaque tissue and provides further insight into PD pathogenesis.

Strengths and limitations: The strength of this pilot study is that it evaluated methylation changes between ED + PD and ED-only individuals using new and updated array analyses. This pilot study is limited due to a cross-sectional design that only examines differential methylation in non-plaque tissues.

Conclusion: Identification of epigenetic differences in non-plaque tissue in men with and without PD suggests systemic changes and provides further insight into the pathogenesis of PD.