Genomic variation in IC/BPS based on bladder capacity

Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) who have low bladder capacity have a significantly different gene expression profile than both IC/BPS patients with normal bladder capacity and those without the condition, researchers reported in a recently published pilot study.

The finding, published online ahead of print in the Journal of Urology, may reflect a difference in disease pathophysiology among IC/BPS patients with low bladder capacity, study authors say.

A leader in the field of IC/BPS called the research "only the beginning of a major effort" to identify markers for the condition.

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“This is the first study to document functional genomic variation based solely on bladder capacity,” said co-author Robert J. Evans, MD, of Wake Forest School of Medicine, Winston-Salem, NC. “Interstitial cystitis is notoriously difficult to diagnose. The identification of biomarkers to improve diagnosis or treatment would be a significant breakthrough for patients and physicians.”

For the study, researchers analyzed bladder biopsies from 13 patients diagnosed with IC/BPS and three patients without the condition. The biopsies were sorted into three groups: low bladder capacity (<13 fluid ounces under anesthesia), bladder capacity >13 ounces, and patients without IC/BPS. Using microarray analysis, the researchers looked for similarities and differences in gene expression between groups.

The results showed a highly significant difference between low-capacity patients and both the normal-capacity patients and controls. The low-capacity patients had genes related to inflammation and immune signaling turned “on.” The results may reflect a fundamental difference in disease processes.

“These gene expression differences may explain why clinical trials for IC are so variable in effectiveness and have a large number of non-responders,” Dr. Evans said. “There may be subtypes of the disease that respond best to particular treatments.”

Based on these early results, the team is conducting further research with the aim of identifying and validating a biomarker to aid in diagnosis and treatment of IC.

“Diseases are rarely seen as single entities anymore,” said senior author Stephen J. Walker, PhD, of Wake Forest Baptist’s Institute for Regenerative Medicine. “Patients demonstrating a specific disease subtype may respond more quickly and or more favorably to treatments that target that specific subtype. Having the ability to identify the right treatment for the right patient is the ultimate goal.”

“This is a very interesting study and only the beginning of a major effort to define markers for this syndrome,” said Philip M. Hanno, MPH, of the University of Pennsylvania, Philadelphia. “Markers will be useful only if they can guide therapy, improve diagnosis, or give us important information on long-term prognosis. We shall see.”

Dr. Hanno, a Urology Times editorial consultant, said the numbers in the Wake Forest study are small and whether the results reflect cause or effect of the disease process is unclear.

“I think that similar larger studies in the future should look at what we now believe is the most prominent phenotype and may indeed be a completely separate disease, namely Hunner lesion disease,” he said. “Similar studies could compare groups of BPS patients with Hunner lesions, without Hunner lesions, patients with overactive bladder, and a normal control group. Eventually, use of the European Society for the Study of Interstitial Cystitis classification to provide a grid for marker studies would be very valuable [Eur Urol 2008; 53:60-7].”

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