Dataset Information

Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.

ABSTRACT: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS. One family has a previously reported SIX5 variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pathogenic heterozygous variant in ATP2A2 (ENST00000539276.2:c.235G>A, p.Glu79Lys) is identified in two unrelated probands, indicating possible Darier-White disease. Two private heterozygous variants are identified in ATP2C1 (ENST00000393221.4:c.2358A>T, p.Glu786Asp (VUS/Likely Pathogenic) and ENST00000393221.4:c.989C>G, p.Thr330Ser (likely pathogenic)), indicative of Hailey-Hailey Disease. Sequence kernel association test analysis finds an increased burden of rare ATP2C1 variants in the IC/BPS cases versus a control cohort (p = 0.03, OR = 6.76), though does not survive Bonferroni correction. The data suggest that some individuals with IC/BPS may have unrecognized Mendelian syndromes. Comprehensive phenotyping and genotyping aid in understanding the range of diagnoses in the population-based IC/BPS cohort. Conversely, ATP2C1, ATP2A2, and SIX5 may be candidate genes for IC/BPS. Further evaluation with larger numbers is needed. Genetically screening individuals with IC/BPS may help diagnose and treat this painful disorder due to its heterogeneous nature.

SUBMITTER: Estrella E

PROVIDER: S-EPMC10000272 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.

Estrella Elicia E Rockowitz Shira S Thorne Marielle M Smith Pressley P Petit Jeanette J Zehnder Veronica V Yu Richard N RN Bauer Stuart S Berde Charles C Agrawal Pankaj B PB Beggs Alan H AH Gharavi Ali G AG Kunkel Louis L Brownstein Catherine A CA

Advanced genetics (Hoboken, N.J.) 20221127 1

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain disorder causing symptoms of urinary frequency, urgency, and bladder discomfort or pain. Although this condition affects a large population, little is known about its etiology. Genetic analyses of whole exome sequencing are performed on 109 individuals with IC/BPS. One family has a previously reported <i>SIX5</i> variant (ENST00000317578.6:c.472G>A, p.Ala158Thr), consistent with Branchiootorenal syndrome 2 (BOR2). A likely pa ...[more]

PMID: 36910591

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Project description:Observational studies suggest that interstitial cystitis/bladder pain syndrome (IC/BPS) indices might be influenced by autoimmune diseases (AIDs), though it is difficult to infer causal relationships based on observational data due to risk of residual confounding. We utilized Mendelian randomization (MR) to explore causal relevance of multiple AIDs on IC/BPS. Our bidirectional two-sample MR analysis was based on summary statistics from the most recent and comprehensive genome-wide association studies. This particular approach was used to delve into the relationships of cause and effect between IC/BPS and a group of 14 AIDs. We examined a range of AIDs such as ulcerative colitis, Crohn disease, celiac disease, Sjogren syndrome, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, primary biliary cirrhosis, psoriasis, asthma, eczema, ankylosing spondylitis, type 1 diabetes, and primary sclerosing cholangitis. Our primary analytical approach involved using the inverse variance weighting method to establish causal relationships across various AIDs and IC/BPS conditions. Furthermore, we carried out additional examinations, such as utilizing the weighted median technique, MR-Egger regression, MR-PRESSO, and evaluating reverse causality, in order to strengthen the dependability of our results. Our findings indicate a strong association between genetically predicted asthma and the risk of developing IC/BPS with a weighted odds ratio of 1.692, a confidence interval of 1.147 to 2.496, and P = .008, while the Cochran Q test P = .589 and the MR-Egger intercept test P = .554, MR-PRESSO global test P = .600. No evidence was found for causal relationships between other AIDs and IC/BPS. Individuals with asthma show an increased vulnerability to IC/BPS according to our findings. More randomized controlled trials are necessary to validate these results. These results underscore the importance for healthcare providers to assess the potential risk in asthma patients, offering a novel genetic perspective on studying interstitial cystitis.

Project description:Purpose of the Meeting:Bladder pain syndrome/interstitial cystitis is a prevalent but underserved disease. At the Global Interstitial Cystitis/Bladder Pain Syndrome Society (GIBS) meeting, the organization and participants were committed to delivering word-class expertise and collaboration in research and patient care. Under the umbrella of GIBS, leading research scholars from different backgrounds and specialties, as well as clinicians, from across the globe interested in the science and art of practice of Bladder Pain Syndrome (BPS)/Interstitial Cystitis (IC) were invited to deliberate on various dimensions of this disease. The meeting aimed to have global guidelines to establish firm directions to practicing clinicians and patients alike on the diagnosis and treatment of this disease entity. Chronic Pelvic Pain Syndrome (CPPS) is defined by pain in the pelvic area that can have different etiologies. This can be due to urologic, gynecologic, musculoskeletal, gastrointestinal, neurologic, and autoimmune or rheumatologic diseases. At the GIBS meeting held in Mumbai, India, in August 2019, a multidisciplinary expert panel of international urologists, gynecologists, pain specialists, and dietitians took part in a think tank to discuss the development of evidence-based diagnostic and treatment algorithms for BPS/IC. Summary of Presented Findings:The diagnosis of BPS/IC is difficult in daily clinical practice. Patients with BPS/IC present with a variety of signs and symptoms and clinical test results. Hence, they might be misdiagnosed or underdiagnosed, and the correct diagnosis might take a long time. A good history and physical examination, along with cystoscopy, is a must for the diagnosis of IC/BPS. For the treatment, besides lifestyle management and dietary advice, oral medication and bladder instillation therapy, botulinum toxin, and sacral neuromodulation were discussed. The innovation in bladder instillation applicators, as well as battery-free neuromodulation through the tibial nerve, was discussed, as well. Recommendation for Future Research:As BPS/IC is complex, for many patients, several treatments are necessary at the same time. This was presented at GIBS 2019 as the piano model. In this way, a combination of treatments is tailored to an individual patient depending on the symptoms, age, and patients' characteristics. In the art of medicine, especially when dealing with BPS/IC patients, pressing the right key at the right time makes the difference.

Dataset Information

Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.

Publications

Mendelian Disorders in an Interstitial Cystitis/Bladder Pain Syndrome Cohort.

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