[ad_1]
Credit: CC0 Public Domain
For the first time, a team of researchers has discovered a specific place in the human genome that increases the risk of erectile dysfunction. This discovery is an important advance in understanding the genetics underlying erectile dysfunction. The study, "Genetic variation in the SIM1 locus is associated with erectile dysfunction", will be published in the review on October 8 Proceedings of the National Academy of Sciences.
Erectile dysfunction, the inability to get and maintain an erection sufficient for sexual activity, is a common and expensive condition in men, mainly of middle and older age. The disease is linked to many causes, such as neurological, hormonal and vascular factors.
Therapies based on these factors exist, but many men do not respond to them. Genetics is also suspected to be a factor in about one third of erectile dysfunction cases, but researchers have so far not established an association with specific genomic sites.
The new study found that variations in a specific genome location, called a genetic locus, close to the SIM1 gene are significantly associated with an increased risk of erectile dysfunction. The researchers ruled out the risk being due to other known risk factors for erectile dysfunction, such as body mass index, or differences in the way men describe their erectile dysfunction. The study also demonstrated a biological role for genetic localization in the regulation of sexual function, strongly suggesting that these variations may cause erectile dysfunction.
"Identifying this SIM1 locus as a risk factor for erectile dysfunction is a big problem as it provides much-needed evidence that there is a genetic component in the disease," said lead author of the study. , Eric Jorgenson, Ph.D., Research Fellow, Kaiser Permanente Northern California Research Division. "The identification of the first genetic risk factor for erectile dysfunction is an exciting discovery because it opens the door to investigations of new genetic-based treatments."
The researchers conducted a genome-wide association study in two large cohorts to study genetic risk factors for erectile dysfunction. The first cohort included 36,648 men from the Adult Health and Aging Research (GERA) cohort, which is part of the Kaiser Permanente Research Program on Genes, Environment and Health, a research program affiliated to the Kaiser Permanente Research Bank. The Research Bank supports internal and external investigations into various health conditions and diseases. It includes biological samples from over 320,000 Kaiser Permanente members who have given their consent, as well as related genetic, environmental and health data.
The GERA cohort included male members of Kaiser Permanente who responded to an inquiry into their condition, received a clinical diagnosis of erectile dysfunction based on their electronic medical record, and used drugs or other erectile dysfunction treatments. . The results of the GERA cohort were then verified in a cohort of 222,358 men from UK Biobank.
The study found that variations in the SIM1 locus were associated with a 26% increase in the risk of erectile dysfunction. This risk was independent of the known risk factors for erectile dysfunction. The association has been replicated in the sample of the UK biobank, providing a solid confirmation of the results.
"This significant advance in our understanding of erectile dysfunction is made possible by the Kaiser Permanente Research Bank's unique ability to link in-depth questionnaires, electronic health records and genetic data to such a large population," Stephen said. Van, lead author of the study. Den Eeden, Ph.D., researcher at the Research Division.
Erectile dysfunction has been difficult to study in part because of differences in how patients report their symptoms. To overcome this challenge, the study sought to determine whether the SIM1 locus was a risk factor when examining differences in the way men reported their erectile dysfunction to their physician. The study found that this place was actually a risk factor for erectile dysfunction, whether the disorder is defined by clinical diagnoses, by the history of prescriptions or by the participant's self-assessment. ;study.
The study then identified a biological role for this site in susceptibility to erectile dysfunction. The SIM1 gene is known to be part of a signaling pathway that plays a central role in the regulation of body weight and sexual function. The erectile dysfunction locus is located near but not in the SIM1 gene. Members of the University of California San Francisco research team were able to demonstrate that the implicated localization physically interacts with the SIM1 gene promoter and that variants of this localization alter the function of a master gene regulator, called activator. .
Think of a gene as a light bulb, said Jorgenson: The promoter is like a switch, and an activator acts as a fuse box. Since the erectile dysfunction risk locus has shown enhancer activity and interacted with the SIM1 promoter, the risk locus of erectile dysfunction probably has an influence on the expression of the SIM1 gene, activating it and disabling it when needed, according to the study.
"The different pieces of evidence that we present in this study fit together like puzzle pieces to give an idea of how the SIM1 locus can control erectile function," said Jorgenson.
The study highlights the potential of SIM1 as a target for the development of new treatments for erectile dysfunction, needed as about half of men trying the currently available pharmaceutical treatments for erectile dysfunction treatment do not answer it.
"This study points to a new research direction on erectile dysfunction that could help us identify other key genetic variants that trigger the disease and conduct investigations to better understand the precise mechanisms by which they work," he said. Hunter Wessells, MD, Chair of Urology. at the University of Washington School of Medicine, co-author and one of the principal investigators of the study. "Hopefully this will result in better treatments and, importantly, prevention approaches for men and their partners who often suffer silently from this disease."
Explore further:
What men need to know about drugs and anesthesia at DU
More information:
Eric Jorgenson et al., "Genetic variation in the SIM1 locus is associated with erectile dysfunction" PNAS (2018). www.pnas.org/cgi/doi/10.1073/pnas.1809872115
Source link
