Urinary incontinence, pelvic prolapse may have genetic basis

Studies are revealing a genetic basis for stress urinary incontinence and pelvic organ prolapse and are showing that the two conditions are more disparate than previously thought.

St. Petersburg, FL-Studies are revealing a genetic basis for stress urinary incontinence and pelvic organ prolapse and are showing that the two conditions are more disparate than previously thought.

Dutch and Swedish twin studies have suggested a genetic component of these two conditions. More recently, Peggy Norton, MD, and colleagues at the University of Utah, Salt Lake City, found more concrete evidence of a genetic basis of pelvic organ prolapse with genome-wide linkage analysis (Am J Hum Genet 2009; 84:678-82). Those studies pointed strongly to an area on chromosome 9 as a major contributor.

Now, Dr. Norton and her team have performed linkage analysis in families with high rates of stress incontinence and found evidence of a genetic basis there, too-but a different one. The most prominent linkage occurs on chromosome 4, according to findings presented at the Society for Urodynamics and Female Urology winter meeting.

"It's reasonable to tell patients that it seems to run in families, but we're still trying to figure it out," said Dr. Norton, who is chief of the urogynecology division of the department of obstetrics and gynecology at the University of Utah School of Medicine.

Findings may aid in prevention

More than that, the findings could allow urologists, urogynecologists, and gynecologists to target patients for early prevention and intervention. For example, there is much debate over whether elective cesarean delivery to prevent these problems is appropriate. Genetic analysis might help target the high-risk group for whom the procedure might be appropriate.

Ultimately, the genetic studies will answer basic questions about the etiology of the conditions, explain why some patients don't respond to certain therapies, and lead to more effective treatments.

To hunt for genes that may be responsible for stress urinary incontinence, the team asked women who underwent surgery for the condition to ask their sisters to fill out questionnaires designed to indicate whether they were also affected. Those who were probably affected were invited to the center for clinical phenotyping, based on demographic questionnaires and examinations for possible clinical markers. The women and their affected sisters also gave blood for DNA analysis, and the researchers sought medical record documentation of surgical procedures.

The researchers performed genome-wide linkage analysis in 40 families with two or more female members who were surgically treated for stress incontinence. Linkage analysis looks for single nucleotide polymorphisms that affected family members share and unaffected members do not, pointing to shared regions of the genome likely containing the responsible genes.

Among these women, the 100 best matches were used for genotyping. The most commonly shared genetic regions occurred on chromosomes 2, 4, 8, 10, and 11, with an especially high probability of a suspect region on chromosome 4.

The investigators hope to get a narrower peak in the shared region and will then start to sequence that area to find the suspect genes, Dr. Norton explained.

The apparent genetic differences in predisposition to stress incontinence and pelvic organ prolapse didn't always mesh with patient's clinical characteristics that would give practitioners clear phenotypes, however. The research team had difficulty finding patients who had only prolapse or stress incontinence, Dr. Norton noted.

Nevertheless, the evidence is growing that stress incontinence is heritable.