The role of genetic variants in Peyronie disease and its correlation with Dupuytren disease

Peyronie (PD) is a fibro-proliferative disorder characterized by abnormal collagen deposition in the tunica albuginea of the penis. In PD, plaque formation results in penile pain, shortening, curvature and loss of rigidity. PD is thought to have a similar disease mechanism as Dupuytren’s disease (DD), in which disease nodules and cords can form in the connective tissue that can cause debilitating flexion contractures of the digits of the hand. Abernathy (London, UK) first reported on their relation in 1828 (1). In the 1960s, it was suggested that PD patients had intercourse more frequently and more vigorously than age-matched cohorts (2), but in scientific practice it was impossible to prove this. However, there is no question that an accident during penetration when the penis bends excessively may induce PD. More recently, it was shown that PD and DD have a familial aggregation (3) and several genetic risk variants are known to be associated (4). In 2004, Qian et al. already demonstrated that the patterns of gene expression alteration of certain genes in DD and PD were similar, indicating a common pathophysiology (5). Biological cell studies identified overlap in patterns of chromosomal aberrations in fibroblasts from PD and DD lesions (6). In 2012, our research group associated nine loci to DD in the first genome-wide association study (GWAS) of DD, and one of these nine loci was also proven to be associated to PD (7). A more recent GWAS discovered 17 additional loci for DD (8). A GWAS has not been performed for PD.  Therefore, in this study we aim to identify genetic variants suggestive for PD through a GWAS. Our group will soon carry out a GWAS for DD as well with the new UGLI data of approximately 63,000 individuals (OV18_0461) and perform a meta-analysis of DD with other cohorts  in order to identify additional DD loci. This also provides possibilities to further explore the genetic correlation of DD with PD.