MP33-11 EVIDENCE FOR HEREDITY OF PEYRONIE’S DISEASE USING A LARGE POPULATION DATABASE

Abstract

INTRODUCTION AND OBJECTIVE: Peyronie's disease (PD) co-aggregates in a small number of first-degree relative pairs (e.g., father - son), suggestive of a genetic etiology in a subset of patients.1 However, the familial aggregation of PD in more distant relatives, as well as the aggregation of Dupuytren's disease (DD) in probands and their relatives has not been thoroughly investigated. Our objective was to explore evidence for familial clustering of PD and DD in close and distant relatives. METHODS: The Utah Population Database, a resource that includes extensive genealogy information linked to electronic medical records (available since 1995) was used to identify men and their relatives with PD and DD using diagnosis codes. All cases were required to have high-quality genealogy data (information available for 12 of 14 of their immediate ancestors). We estimated relative risk (RR) of PD in first- through fifth-degree relatives. We also investigated the average relatedness of cases compared to 1,000 sets of controls matched on sex, 5-year birth-cohort and birth in/out of Utah. All data involved in this project were de-identified and waivers of informed consent granted by the Institutional Review Board. RESULTS: Analyses were conducted on 307 individuals with PD, and their first- through fifth-degree relatives. Mean age of diagnosis for men with PD was 56.4 years. RR estimates were significant for firstdegree relatives (observed 6 PD cases, expected 0.83 cases, RR=7.24, 95% CI=2.66-15.75, p=2.23e-4) and fifth-degree relatives (observed 30 PD cases, expected 20.37 cases, RR=1.47, 95% CI=1.06-2.10, p=0.036). The average relatedness of cases was significantly greater than matched controls (p=0.001), even after removing first- and second-degree relatives (p=0.017) as a further investigation of the familial clustering of PD in distant relatives (see graph). We observed a significantly increased risk of DD (RR=8.34, 95% CI=2.27-21.35, p=1.51e-3) among PD probands but not among their relatives. CONCLUSIONS: Significant excess relatedness was observed for both close and more distant relationships for some PD cases, strongly supporting a genetic contribution to the pathogenesis of PD in at least a subset of PD cases. An increased risk of DD in self suggests that shared genes, environment, or both contribute to these disorders. (Figure Presented).