Gene variants linked to overactive bladder and prolapse in women

By Nikki Withers, medwireNews Reporter

A systematic review and meta-analysis of genetic association studies reveals a number of genetic variations associated with overactive bladder and pelvic organ prolapse in women.

The UK researchers found significant associations between a variation in the gene coding for beta 3 adrenoreceptor (ADRB3) and overactive bladder, and a variation in the gene coding for collagen type 3 alpha 1 (COL1A1) and prolapse.

However, the authors caution that genetic testing for these single nucleotide polymorphisms “cannot be recommended based on the current evidence”.

The study examined which polymorphisms, genes, or both had been tested for an association with pelvic organ prolapse or lower urinary tract symptoms (LUTS) in women, and assessed the strength, consistency, and potential for bias, among published associations.

In total, data from 27 published and seven unpublished studies were included.

Analysis was possible for 11 polymorphisms in or near seven genes: ADRB3, COL1A1, COL3A1, laminin gamma 1 (LAMC1), matrix metalloproteinase (MMP)1, MMP3 and MMP9.

This revealed that presence of the rs4994 polymorphism of the ADRB3 gene increased the likelihood of overactive bladder 2.5-fold.

And the likelihood of prolapse or stress urinary incontinence increased 1.3- and 2.1-fold, respectively, in women with the rs1800012 polymorphism of the COL1A1 gene, report Rufus Cartwright (Imperial College London) and colleagues in the American Journal of Obstetrics and Gynecology.

Other meta-analyses, including those for polymorphisms of COL3A1, LAMC1, MMP1, MMP3 and MMP9 did not show significant effects.

The researchers note that, because they included studies with varying diagnostic criteria, there may be considerable disparity between symptomatic and objective findings for both LUTS and prolapse.

“In the future, genetic counseling may play one part of advice about risks of mode of delivery, and may help target women for primary or secondary prevention,” the researchers conclude.

They suggest that clinicians should still use a family history of prolapse or incontinence as a simple marker of future risk, “with clearly documented interactions with modifiable risk factors such including parity, vaginal childbirth, and obesity.”

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