PD01-05 SIGNIFICANT LINKAGE EVIDENCE FOR INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME ON CHROMOSOME 3

Abstract

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Interstitial Cystitis I1 Apr 2017PD01-05 SIGNIFICANT LINKAGE EVIDENCE FOR INTERSTITIAL CYSTITIS/PAINFUL BLADDER SYNDROME ON CHROMOSOME 3 Kristina Allen-Brady, Kerry Rowe, Melissa Cessna, and Peggy Norton Kristina Allen-BradyKristina Allen-Brady More articles by this author , Kerry RoweKerry Rowe More articles by this author , Melissa CessnaMelissa Cessna More articles by this author , and Peggy NortonPeggy Norton More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.185AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain condition with unknown etiology. Family history is one of the strongest known risk factors, suggesting a genetic contribution. 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 for IC/PBS. METHODS Using the Utah Population Database (a population-based genealogy resource linked to medical records at the largest Utah healthcare provider), 13 high-risk pedigrees (defined as having a statistical excess (p<0.05) of IC/PBS cases among relatives who were hospital patients compared to expected number of cases using age- and sex-matched hospital rates for IC/PBS) were used for this analysis. Each pedigree had at least two sampled cases; case status was confirmed in the medical record using natural language processing. DNA was obtained from stored, non-cancerous, formalin-fixed, paraffin-embedded (FFPE) tissue blocks (e.g., appendix). Pedigrees ranged in size from 2 to 12 genotyped cases (n=48). Genotype data were obtained from Illumina OmniExpress BeadChip array (~710, 0000 SNPs); all SNPs passed quality control filters prior to linkage analysis. We eliminated highly correlated SNP markers (i.e., high linkage disequilibrium). Parametric linkage analysis using general dominant and recessive models was performed using the Markov Chain, Monte Carlo linkage analysis method, MCLINK. Results are reported as heterogeneity logarithm of odds scores (HLODs), defined as suggestive (HLOD ≥ 1.86) and significant (HLOD ≥ 3.3) linkage evidence. We also reported the number of individual pedigrees considered ″linked″ to a significant genomic peak (i.e., pedigree LOD score ≥ 0.588). RESULTS Significant genome-wide linkage evidence was found on chromosome 3p21-3q13 with a maximum HLOD score of 3.56 under a dominant model. There were 4 pedigrees (30.8%) that had at least nominal linkage evidence (LOD ≥ 0.588) in this region. The most informative pedigree for linkage included 12 IC/PBS cases and had an individual LOD score of 2.1 in this region. Other regions with suggestive evidence for linkage included 1p21-1q25, 4q12-13, 9p24-22, and 14q24, all under a dominant model. CONCLUSIONS While the etiology of IC/PBS is unknown, this study provides evidence that a genetic variant(s) on chromosome 3 likely contributes to IC/PBS predisposition. Further study of the pedigrees underlying this significant linkage evidence and sequence analysis of the affected cases may provide insight into genes contributing to IC/PBS. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e47-e48 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Kristina Allen-Brady More articles by this author Kerry Rowe More articles by this author Melissa Cessna More articles by this author Peggy Norton More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...