Potential Gene Biomarkers for OAB Identified

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TORONTO—An analysis of gene-expression patterns in women with overactive bladder (OAB) may point the way to possible new biomarkers for the condition.

At the 2010 joint meeting of the International Continence Society and the International Urogynecological Association, researchers presented data from a whole-genome microarray analysis showing that 1,115 genes are expressed at much higher or lower levels in women with OAB than controls with stress urinary incontinence.

Whole-genome microarray analysis is sometimes described as providing a molecular ‘portrait' of a particular pathological sample. It provides a graphic representation of the expression level of tens of thousands of genes, and indicates which ones are expressed much more or much less than others.

The gene that had the greatest increase in expression was that coding for the M3 muscarinic receptor. The researchers discovered that it is expressed at levels 4.23 times greater in women with OAB than in controls. Investigators also found that the gene for the ryanodine receptor 2 (RYR2), an important regulator of beta-adrenergic signaling, was expressed at 3.52 times higher levels than in controls.

“There's a lot of interest at the moment in beta-adrenergic signaling in OAB, particularly because there's a new drug coming to the market next year, mirabegron, that is a beta-adrenergic receptor agonist,” lead investigator Rufus Cartwright, MBBS, told Renal & Urology News. “RYR2 has never before been shown to be expressed in the bladder—but the fact that we found it is expressed there in OAB, and at high levels, indicates that it may in fact be a key regulator of bladder contractility.”

Dr. Cartwright, an academic clinical fellow in the Department of Urogynaecology, Imperial College London, cautioned that the results are only preliminary and that the approach can never be used directly in clinical practice.

“It's very expensive—it costs more than $1,000 per patient,” he said. “And there are statistical issues with this type of analysis: some of what we saw are true signals and some are just statistical anomalies. … But our study does indicate immediately what some of the potential markers are for OAB.”          

The team will try to reproduce the results for the 29 genes that were the most over- or under-expressed in women with OAB compared with controls. They will use quantitative real-time polymerase chain reaction, which both detects and quantifies specific DNA or RNA sequences.

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