WNT2 Locus is Involved in Genetic Susceptibility of Peyronie’s Disease

Abstract

Introduction Peyronie’s disease (PD) is a fibromatosis of the penis, with a pathology very similar to what is seen in the hand (palmar fascia) in Dupuytren’s disease (DD). Recently, we performed a genome-wide association study and identified nine genetic loci containing common variants associated with DD. Seven of these loci mapped within or near genes of the canonical WNT pathway and each locus yielded relatively large odds ratios (ORs) for DD disease status. Aim Given the clinical overlap between PD and DD, we examined whether the nine DD susceptibility loci are also involved in PD. Methods An association study was performed using a case/control design. From 2007 to 2010, we prospectively included 111 men who had been clinically diagnosed with PD. Control subjects (N = 490 males) were randomly drawn from a population-based cohort from the same region of the Netherlands. Allele frequencies in the 111 PD cases and 490 controls were compared using a 1-degree-of-freedom basic chi-square test. A P value < 0.05 after Bonferroni correction for the nine tested single nucleotide polymorphisms (SNPs) was considered statistically significant (i.e., P < 0.0056). Main Outcome Measure Association of genetic markers (SNPs) with PD. Results We observed significant association with SNP rs4730775 at the wingless-type MMTV integration site family member 2 (WNT2) locus on chromosome 7 (P = 0.0015, OR 0.61), but found no evidence for the other eight loci being involved with PD despite the large effect size seen for some of these variants in DD. The WNT2 association was even more significant after we removed 15 patients with comorbid DD. Conclusions WNT2 is a susceptibility locus for PD and our finding provides evidence for a partly shared genetic susceptibility between PD and DD.

The Genetic Basis of Peyronie Disease: A Review

“…In order to determine whether these SNPs were also present in men with PD, allele frequencies for the SNPs were assessed among 111 men with PD and compared to 490 unaffected controls. 45 Of the SNPs evaluated, a statistically significant association was observed with SNP rs4730775 at the WNT2 locus on chromosome 7. Taken together, these studies further implicate a common set of genetic factors for both PD and DD.…”

Intralesional hyaluronic acid: an innovative treatment for Peyronie’s disease

“…The lesion caused by PD consists of a scar containing a large amount of collagen and fibrin, but the exact etiology is uncertain. Currently the most credible etiopathogenetic theories are: the genetic hypothesis [5,6] (PD is often associated with Dupuytren's disease (palmar aponeurosis), which is histologically similar and identified by an autosomal dominant gene with variable expressivity);…”

Recent Pathophysiological Aspects of Peyronie’s Disease: Role of Free Radicals, Rationale, and Therapeutic Implications for Antioxidant Treatment—Literature Review

“…Familiar aggregation and genetic transmission through HLA-B7 antigens had been amply described and understood [6–8]. Recently, a genetic locus that PD shares with Dupuytren's contracture was identified; WNT2 is the locus involved in genetic predisposition for both Dupuytren's disease and PD [9]. Previously, some studies had already observed the analogy and strong affinity between the two diseases: Dupuytren's contracture's typical cells with “cross-banded” nuclei had been observed in PD plaques in 1976; in 1989, Somers et al, after histological examination of PD plaques, proved an increase in type III collagen content, similarly to what occurs in Dupuytren's contracture [10, 11].…”