Unpleasant to unbearable and somehow embarrassing: Millions of people make life difficult for hemorrhoids – yet the widespread disease has so far hardly been researched. But now, for the first time, a genetic study has provided fundamental insights into the mechanisms and causes of the disease. The results have potential for the development of therapies and preventive measures for patients and risk groups, say the scientists.
Colloquially, the condition is often referred to as “hemorrhoids”, but everyone has them. Only the pathologically altered versions of these tissue structures are the problem. The hemorrhoids are used to close the anus and control bowel movements. In the case of hemorrhoidal disease, these blood-filled cushions begin to enlarge and expand. This causes itching and burning, and in more advanced stages it can lead to severe pain and bleeding. In these cases, surgical treatment is often necessary. It is clear that large parts of the population are affected by hemorrhoids, but precise information is not available. Because it is a disease that those affected do not like to talk about.
Amazingly unexplored popular suffering
This taboo may also be one of the reasons why the basics of the molecular mechanisms and tendencies to hemorrhoid disease have so far been little researched. Known risk factors include obesity, a low-fiber diet and frequent sitting. In addition, excessively long visits to the toilet, pressing too hard, and lifting heavy objects are known risk factors. However, so far there is no clear scientific knowledge about the background to these factors. As has now been done for many other diseases, an international research team has now sounded out the genetic predispositions that are associated with the risk of developing hemorrhoidal diseases.
The scientists compared the genetic makeup of 218,920 patients with the genetic information of 725,213 comparators. The analyzes enabled them to identify 102 regions in the human genome that contain genes that play a role in the development of hemorrhoids. For the first time you have circled so-called risk genes. This means that if people have certain versions of these genes, they have an increased tendency to develop the disease. In addition, the researchers analyzed cells from hemorrhoid tissue samples taken during operations. In doing so, they identified the products that the newly discovered risk genes are responsible for manufacturing directly at the scene.
Genetic insights into basics
For the first time, the scientists gained fundamental information about which functions may be disrupted in the disease and lead to the symptoms. “Our results suggest that hemorrhoid disease is at least partially the result of a malfunction of the smooth muscles, blood vessels and connective tissue in this area. We have thus gained initial indications of possible disease mechanisms of the widespread disease. In the long term, a better understanding could help in the development of additional non-invasive therapy options and lead to opportunities to tackle the causes of the disease directly, ”says co-author Andre Franke from the University of Kiel.
As part of their study, the scientists have also already developed so-called polygenic risk scores (PRS) based on the identified risk genes. For combinations of several risk genes, these values indicate the respective degree of propensity to haemorrhoidal disease. To check whether these risk values actually provide useful information, the researchers applied them to genetic data from people who were initially not aware of any diagnoses. The subsequent comparison of the calculated risk scores with the patient data confirmed the correlation: Of the 180,435 people analyzed, those who were particularly recently ill or who had to undergo operations more frequently had particularly high risk scores. “In the future, these analyzes could therefore help to identify people at an increased risk for severe manifestations at an early stage and to provide them with better support. You could also possibly particularly benefit from a preventive lifestyle, ”says co-author Volker Kahlke.
The “price” for walking upright?
As part of the study, two of the researchers involved also dealt with the topic more fundamentally. In addition to the background to the disease, little is known about the hemorrhoids themselves. Thilo Wedel and Francois Cossais from the Anatomical Institute of the University of Kiel have therefore now carried out investigations that should clarify to what extent the anal blood vessel cavernous bodies are typical for humans. Their studies of tissue samples from a gorilla and a baboon as well as mice showed: “While humans have very well developed hemorrhoidal cushions, these are less pronounced in gorillas and even more so in baboons and are no longer found in mice. The special formation of the hemorrhoids in humans is probably due to the upright gait, for which a secure anal canal closure is particularly important, ”explain Wedel and Cossais.
Source: Christian-Albrechts-Universität zu Kiel, specialist article: Good, doi: 10.1136 / gutjnl-2020-323868