Interstitial cystitis (IC) comprises severe bladder pain and urinary frequency and urgency, has objective diagnostic findings, and its pathogenesis is unknown. We have shown that first-degree relatives of IC patients have a relative risk of > 16. That this familial aggregation is not solely an environmental effect is reflected by our further findings of significantly greater concordance among monozygotic than dizygotic twins and occurrence of IC in 2nd and 3rd degree relatives who presumably have not shared households. Hypothesizing that alleles for IC are inherited in these families, we will recruit multiplex families, i.e. those with greater than or equal too 2 first degree relatives who meet NIDDK criteria for IC, via a national recruitment campaign directed at urologists, employing the Internet, and collaborating with the Interstitial Cystitis Association. Pedigrees will be constructed with family members assigned to intermediate categories of IC. We will perform linkage analysis seeking loci of susceptibility to IC. We estimate that >900 probands will be evaluated. Reasonable assumptions of eligibility and volunteer rates suggest we will enroll >450 multiplex families with >2400 family members donating DNA. To date, a survey has already identified 101 potential probands; 143 unsolicited, additional potential probands have contacted us. Parametric, non-parametric, and conditional analyses will be performed with attention to subgroups to maximize homogeneity and to intermediate categories to avoid misclassification. The large number of participants will provide substantial power. We will finely map linkage regions and perform family-based linkage and association tests. In parallel we will help to discover additional multiplex families for extension/replication studies. These data on pedigrees and genotypes and stored DNA, from properly informed participants, will be a valuable resource. The identification of alleles of susceptibility to IC may reveal clues to pathogenesis, clinical therapy, preventive strategy, and possibly gene therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01DK066136-04
Application #
7126805
Study Section
Special Emphasis Panel (ZRG1-UROL (51))
Program Officer
Rasooly, Rebekah S
Project Start
2003-09-30
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
4
Fiscal Year
2006
Total Cost
$507,388
Indirect Cost
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Warren, John W; Clauw, Daniel J; Wesselmann, Ursula et al. (2014) Functional somatic syndromes as risk factors for hysterectomy in early bladder pain syndrome/interstitial cystitis. J Psychosom Res 77:363-7
Warren, John W; Morozov, Vadim; Howard, Fred M et al. (2014) Before the onset of interstitial cystitis/bladder pain syndrome, the presence of multiple non-bladder syndromes is strongly associated with a history of multiple surgeries. J Psychosom Res 76:75-9
Warren, John W; Clauw, Daniel J; Langenberg, Patricia (2013) Prognostic factors for recent-onset interstitial cystitis/painful bladder syndrome. BJU Int 111:E92-7
Warren, John W; Howard, Fred M; Morozov, Vadim V (2013) Is there a high incidence of hysterectomy and other nonbladder surgeries before and after onset of interstitial cystitis/bladder pain syndrome? Am J Obstet Gynecol 208:77.e1-6
Warren, John W; Langenberg, Patricia; Clauw, Daniel J (2013) The number of existing functional somatic syndromes (FSSs) is an important risk factor for new, different FSSs. J Psychosom Res 74:12-7
Warren, John W; Clauw, Daniel J (2012) Functional somatic syndromes: sensitivities and specificities of self-reports of physician diagnosis. Psychosom Med 74:891-5
Warren, John W; Horne, Linda; Diggs, Christina et al. (2011) Nocturia in interstitial cystitis/painful bladder syndrome. Urology 77:1308-12
Warren, John W; van de Merwe, Joop P; Nickel, J Curtis (2011) Interstitial cystitis/bladder pain syndrome and nonbladder syndromes: facts and hypotheses. Urology 78:727-32
Warren, John W; Diggs, Christina; Horne, Linda et al. (2011) Interstitial cystitis/painful bladder syndrome: what do patients mean by ""perceived"" bladder pain? Urology 77:309-12
Warren, John W; Wesselmann, Ursula; Morozov, Vadim et al. (2011) Numbers and types of nonbladder syndromes as risk factors for interstitial cystitis/painful bladder syndrome. Urology 77:313-9

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