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October 23, 2018

The Blue Gene

Men with variations in a particular stretch of DNA are more likely to have erectile dysfunction.

Genetics are believed to cause about one-third of all cases of erectile dysfunction (ED), but no confirmed genetic risk factor has ever been found. Drug side effects, cardiovascular issues and other health problems can also contribute to erectile difficulties. Recently, researchers discovered the precise location of genetic variations that increase the risk of erectile dysfunction for a large proportion of men. Having a specific genetic site to home in on raises the promise of new treatments for ED.

The culprit lies near, but not in, a gene called SIM1, in a stretch of DNA known as an enhancer.

A Genetic Switch is Flipped

Genes are best known for producing specific proteins. But how active a gene is and whether it is actually on or off is often determined in other regions of the DNA. If you think of a gene as a light bulb, there is a small region of DNA near the gene called a promoter that functions like a light switch, effectively deciding whether the gene is on or off.

Likewise, there are areas called enhancers, which may lie near the gene or be far away from it. They are sometimes called master gene regulators and function like a fuse box or circuit breaker. They also need to be on for the light switch — promoter — to work and for its gene to be active.

Men who had variations in this stretch of DNA had a 26 percent increased risk of erectile dysfunction.

Researchers from the University of California San Francisco, the University of Washington and Kaiser Permanente located an enhancer for the SIM1 gene. SIM1 variations can basically turn the light switch off, leading to an increased chance of erectile dysfunction (ED). Men who had variations in this stretch of DNA had a 26 percent increased risk of erectile dysfunction.

The study looked at 36,548 men in the United States and confirmed these findings on 222,358 men from the UK. In the U.S. portion of the study, men were given four possible descriptions of their erectile ability — always, usually, sometimes or never able to get and keep an erection good enough for sexual activity. Men who answered sometimes or never were classified as having ED.

Nearly 30 percent of the men in the study had a clinical diagnosis of ED. This allowed the researchers two different ways of comparing their genetic findings to men's sexual function and measuring how strongly variations at this genetic site affected their sexual performance.

About half of all men who try pharmaceutical treatments for erectile dysfunction don't respond to them.

The gene's effects appear unrelated to body mass index (BMI). High BMI is a known risk factor for ED.

About half of all men who try pharmaceutical treatments for erectile dysfunction don't respond to them. This finding gives them a new direction to look in for some relief.

The study appears in PNAS, Proceedings of the National Academy of Sciences and is open access.

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