Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pelvic pain condition with unknown etiology. We hypothesized that related IC/PBS cases were more likely to have a genetic etiology. The purpose of this study was to perform a genetic linkage analysis.
IC/PBS cases were identified using diagnostic codes linked to a population-based genealogy resource (Utah Population Database) and electronic medical records. For this analysis, 13 high-risk pedigrees (defined as having a statistical excess number of IC/PBS cases among descendants compared to matched hospital population rates) were used. Case status was confirmed in medical records using natural language processing. DNA was obtained from stored, non-neoplastic, formalin-fixed, paraffin-embedded (FFPE) tissue blocks. Each pedigree had at least two cases with DNA available. Parametric linkage analysis was performed.
Pedigrees ranged in size from 2 to 12 genotyped cases (n=48 total cases). Significant genome-wide linkage evidence was found on chromosome 3p13-p12.3 (maximum hetTLOD = 3.56) under a dominant model. There were 2 pedigrees with at least nominal linkage evidence (LOD >0.59) in this region; the most informative pedigree included 12 IC/PBS cases (pedigree TLOD = 2.1). Other regions with suggestive linkage evidence included 1p21-q25, 3p21.1-p14.3, 4q12-q13, 9p24-p22, and 14q24-q31, all under a dominant model.
While the etiology of IC/PBS is unknown, this study provides evidence that a genetic variant(s) on chromosome 3, and possibly chromosomes 1, 4, 9, and 14, contribute to IC/PBS predisposition. Sequence analysis of affected cases in identified pedigrees may provide insight into genes contributing to IC/PBS.
The Journal of urology. 2017 Jul 19 [Epub ahead of print]
Kristina Allen-Brady, Kerry Rowe, Melissa Cessna, Sara Lenherr, Peggy Norton
Division of Genetic Epidemiology, Department of Internal Medicine; University of Utah; Salt Lake City, Utah, USA. Electronic address: ., Homer Warner Center for Informatics Research, Intermountain Healthcare, Salt Lake City, Utah, USA., Department of Pathology, Intermountain Healthcare Central Region and Intermountain Healthcare BioRepository, Salt Lake City, Utah, USA., Division of Urology, Department of Surgery; University of Utah, Salt Lake City, Utah USA., Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics and Gynecology; University of Utah, Salt Lake City, Utah, USA.