December 8, 2021
Science

Is Ulcerative Colitis Genetic

Ulcerative Colitis has the highest prevalence in North American and Northern Europe
By
Tomohiro Takano

Ulcerative colitis (UC) is a form of chronic digestive disease. This condition is characterized by irregular inflammation of the inner surface of the colon and rectum. Patients most often experience bloody diarrhea and abdominal pain. Anemia, fever, and weight may also occur. The symptoms of ulcerative colitis tend to appear slowly before becoming more severe. The cause of UC is unknown, but most experts suspect it is a combination of genetic, immune response, and environmental factors.

Researches have shown that genes appear to increase the risk of developing UC. However, while the level of impact is unknown because there are many genetic factors involved, the chance that you will develop UC increases if you have a close family member with ulcerative colitis. A few types of research found that 1 in 4 people have a family history of ulcerative colitis. Another indication that ulcerative colitis is associated with hereditary factors is that the disease is more likely to appear in a particular ethnic population.

Several dozens of variants are believed to contribute to this condition, with many involved in the protective barrier of the intestines. The barrier shields the tissues against the toxins that pass through your digestive system and bacteria that live in your gut. And when this barrier breakdown, it may lead to the immune response that eventually causes ulcerative colitis. Gene mutations linked to the immune system are also likely to foster ulcerative colitis.


Genetic Risk and Ulcerative Colitis


Studies of twins and families are helpful when trying to understand whether a particular disease has genetic components due to children inheriting chromosomes from their parents. With identical twins, children inherit the same genetic makeup as each other. Do they share the same genes? You could expect them to develop equivalent genetic conditions. If one of the twins develops a certain health condition and the other doesn’t, external factors are believed to influence.


Twin and family studies showed that only about 10% of the people living with ulcerative colitis have family members with a history of inflammatory bowel diseases (IBDs). The research shows that people who have a parent, child, or sibling with ulcerative colitis also have higher chances of developing the disease. These people are 4 times more likely to develop ulcerative colitis than the average person.


However, these studies also show that many people who have high genetic risk factors that increase their vulnerability to UC never develop it. In other words, your genes alone can’t be used to predict whether you will develop ulcerative colitis. Still, genetics can give clues about the location, types, and severity of ulcerative colitis symptoms in those who develop the disease.


A meta-analysis study showed that the presence of informative genes and the way they are expressed could show whether your ulcerative colitis is likely to start in the colon or the rectum. The susceptibility genes usually have roles in the intestinal epithelial cell function, immune response, or gut mucosal barrier. According to studies, these genes are displayed differently from those with ulcerative colitis compared to those who don’t have the disease.


Genes Associated With Colitis Genetic


Experts have looked at several genetic changes that may be involved in ulcerative colitis. While they still don’t know how these genetic changes might result in UC, they have a few theories. Other genes linked to ulcerative colitis affect T cells. These T cells work with the immune system to identify bacteria and other foreign intruders and attack them. Some genetic makeups may cause T cells to either wrongly attack the bacteria that usually live in your intestine or are too aggressive to the response of toxins or pathogens passing through the colon. And the response of this immune system may contribute to developing ulcerative colitis.


A study from 2012 discovered more than seventy susceptibility genes for Inflammatory Bowel Disease (IBD). These genes have already been linked to other immune disorders such as ankylosing spondylitis and psoriasis.


IL23 (Interleukin 23) gene was initially discovered as a CD susceptibility, but it has now been confirmed in ulcerative colitis. Similarly, other members of the IL23 signaling pathway, including STAT3, JAK2, and IL12B, have consequently been linked to CD40 and then ulcerative colitis, suggesting that defective IL23 signaling poses a risk to Inflammatory bowel disease as a whole. ECM1 (Extracellular Matrix Protein 1) was indicated in a study as a key event and an active contributor behind intestinal inflammation in IBD. The study shows that the participation of adhesion molecules plays a significant role in the adherence of macrophages and lymphocytes to endothelial cells supporting chronic inflammation in patients with UC.


Environmental Risk Factors


While genes play a significant role in the development of ulcerative colitis, they are just a part of the puzzle. Many people who develop ulcerative colitis have no family history. Environmental factors are likely important to UC development, and more environmental factors also trigger the condition.

It is not currently known if or how triggers work together or relate to other potential environmental factors to cause UC, but it is thought that more than one is likely involved. Some environmental factors include smoking, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), Antibiotics, Contraceptive Pill, and Geographic Location.


Epidemiology


UC has the highest prevalence in North American and Northern Europe, suggesting that a Western diet plays a vital role in UC. The disease has a case of 9 to 20 per one hundred persons in a year, and its occurrence is 156 situations per one hundred persons in a year. Out of the inflammatory bowel diseases, UC is more common in adults. The age of inception is usually between 15-30 years, with the 2nd onset between 50-70 years. Many studies also suggest that ulcerative colitis uniformly affects both men and women. It has been shown that removing the appendix before the age of 20 is linked to a decreased risk of UC.


References:

https://academic.oup.com/ibdjournal/article/17/3/831/4634306

https://www.nhs.uk/conditions/ulcerative-colitis/causes/

https://www.frontiersin.org/articles/10.3389/fphys.2019.00662/full

https://www.jci.org/articles/view/116613




Tomohiro Takano
Tomohiro Takano
Co-Founder and CEO