Genetic variants linked to lower urinary tract symptoms in African-Americans

September 1, 2013

In a study of African-American men, researchers say they’ve linked two genetic variants to severity of lower urinary tract symptoms related to BPH, giving scientists insight into the higher risk facing African-Americans.

San Diego-In a study of African-American men, researchers say they’ve linked two genetic variants to severity of lower urinary tract symptoms related to BPH, giving scientists insight into the higher risk facing African-Americans.

It’s not clear whether the genetic variants are directly or indirectly related to the severity of the symptoms or have nothing to do with them. However, previous research has linked them to the severity of a well-characterized lower urinary tract symptom phenotype.

Future research “could help guide us in screening to tell us who deserves attention because they have biomarkers that indicate an increased risk of bothersome urinary symptoms. It could also help guide treatment by giving us indications about whether early medical intervention with surgery will be advantageous,” first author Brian T. Helfand, MD, PhD, told Urology Times.

“Finally, the genetic biomarkers could also be used to possibly distinguish which men are most at risk of urinary symptoms related to benign prostatic hyperplasia from those at risk of prostate cancer,” added Dr. Helfand, clinical instructor of urology at NorthShore University Health System in Evanston, IL. He presented the findings at the AUA annual meeting in San Diego.

Scientists already suspect that benign growth of the prostate has a genetic component. So what about the LUTS associated with it, such as frequent urination, urgency, and slow urinary streams? And could a genetic trait be more or less common in African-American men, who suffer more from these symptoms?

Dr. Helfand and his co-authors have already discovered six single nucleotide polymorphisms (SNPs) that are linked to the likelihood of severe LUTS and BPH medication use in Caucasian men.

SNPS are “common variations,” Dr. Helfand said, that are present but don’t cause major disruptions in proteins. Still, scientists think they play a role in complex diseases like those that cause urinary symptoms.

There’s another twist: Researchers know that men with these urinary symptoms are at higher risk of prostate cancer. It’s possible that some genetic variants predispose men to both prostate cancer and urinary symptom severity, while others predispose only to prostate cancer or only to symptomatic BPH, Dr. Helfand said.

The authors studied the genomes of 620 African-American volunteers and prospectively tracked their AUA Symptom Index.

Two SNPs associated with symptom severity

Analyses determined that two SNPs, rs10934853 on chromosome 3q21 and rs445114 on chromosome 8q24, were inversely associated with severity of the symptoms and one, rs5945572 on chromosome Xp11, was positively associated. After adjusting for the presence of the other genetic variants and age, rs5945572 (OR=1.33, 95% CI: 1.04-1.71) remained significantly associated with increased urinary symptoms, while rs445114 was associated with marginally decreased urinary symptoms (OR=0.78; 95% CI: 0.60-1.00).

What's next? Researchers need to understand the interplay between the genetic traits and figure out how they explain the difference in the level of risk of symptoms in both African-American and Caucasian men, Dr. Helfand said. The challenge, he said, is that “these variants can interact in complex ways.”

Ultimately, Dr. Helfand said, a major genetic study needs to be performed that will be devoted to urinary symptoms and compare the genotypes between men with and without severe urinary symptoms.UT

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