Ulcerative Colitis (Anderson, 2011) – Is ulcerative colitis genetic?

Man in stomach pain ulcerative colitis

Nebula Genomics DNA Report for Ulcerative Colitis

Is ulcerative colitis genetic? We created a DNA report based on a study that attempted to answer this question. Below you can see a SAMPLE DNA report. To get your personalized DNA report, purchase our Whole Genome Sequencing!

Sample report on ulcerative colitis from Nebula Genomics
Sample variants of ulcerative colitis from Nebula Genomics
To learn more about how Nebula Genomics reports genetic variants in the table above, check out the Nebula Research Library Tutorial.

Introduction to Ulcerative Colitis

Part 1 of Is ulcerative colitis genetic?

Ulcerative colitis (UC) is a chronic inflammatory, digestive disease of the colon and rectum where these areas in the GI tract experience inflammation and ulcers. Patients most often experience abdominal pain and diarrhea mixed with blood. Weight loss, fever, and anemia may also occur. The symptoms tend to start gradually, before becoming more serious in nature. 

The cause of ulcerative colitis is unknown but most doctors suspect it is a combination of genetic and environmental factors, including changes to the normal gut bacteria. It is slightly more common in the developed world, suggesting that a western diet and lifestyle plays an important role in the environmental drive of the disease. 

The condition is one of the inflammatory bowel diseases (IBDs) along with Crohn’s disease and microscopic colitis. 

Inflamed areas in Crohn's disease and ulcerative colitis
Inflamed areas in Crohn’s disease (left) and ulcerative colitis (right). Wikipedia. CC-Attribution-Share Alike 4.0 International.

Diagnosis can be performed with either a colonoscopy, tissue biopsy, or both. Although the condition itself cannot be cured, there are several treatments aimed at reducing the symptoms. One of the most simple treatment options is a change in diet to high calorie or lactose free foods. Certain medications are also available. If the condition is particularly bad, your doctor may also recommend surgery to remove the colon and/or rectum.

Types

Types of the condition are classified based on how much of the rectum and large intestine (colon) are affected.

Types of ulcerative colitis
Types of ulcerative colitis. IBD Relief. Flickr.
  • Ulcerative proctitis: Inflammation is confined to the area closest to the anus (rectum)
  • Proctosigmoiditis: Inflammation involves the rectum and the lower end of the colon
  • Left-sided colitis: Inflammation extends from the rectum up through the sigmoid and descending colon
  • Extensive: Inflammation often affects most of the colon and rectum 
  • Total: Inflammation affects the entire colon and rectum

Is Ulcerative Colitis Genetic?

Inherited genes seem to increase the risk of developing ulcerative colitis. 

Although the inheritance pattern of the condition is unknown due to the fact that many genetic and environmental factors are involved, having a close family member with the disease does increase the likelihood that you will develop it as well. Some studies have found that 1 in 4 patients also have a family history of the condition. Another sign that the condition is linked to hereditary factors is that it is more likely to occur in certain ethnic populations.

Scientists have identified several dozen variants that may contribute to the condition. Many of them are involved in the protective barrier of the intestines. This barrier protects tissues from bacteria that live in the gut and toxins that pass through the digestive system. A breakdown of the barrier may lead to the immune response that ultimately causes the condition. 

Gene mutations in genes related to the immune system are also likely to promote the disease. Some known genes associated with ulcerative colitis are IL23R, which codes for a protein embedded on the outside of certain immune cells called T cells, and IRF5, which codes for a transcription factor that activates other parts of the immune system, including interferons and other cytokines. 

Epidemiology

Part 2 of Is ulcerative colitis genetic?

Ulcerative colitis has the greatest prevalence in Northern Europe and North America, suggesting that a western diet plays a role in the disease. Ulcerative colitis has an incidence of 9 to 20 cases per 100,000 persons per year. Its prevalence is 156 to 291 cases per 100,000 persons per year. Of the IBDs, ulcerative colitis is more prevalent in adults while Crohn’s disease is more common in children.

The typical age of onset is between 15-30 years, with a second onset between 50-70 years. Most studies suggest that the condition equally affects both men and women. 

The removal of the appendix (appendectomy) before the age of 20 has been shown to be associated with a decreased risk of ulcerative colitis. This is the opposite pattern for Crohn’s disease. 

Symptoms of Ulcerative Colitis

Part 3 of Is ulcerative colitis genetic?

The inflammation that causes the condition starts in the rectum and may spread to the colon. 

Symptoms tend to be episodic, meaning that a patient will have periods of symptoms, known as flare ups, followed by times of remission, when no symptoms are present. 

Symptoms often start mild and then progress over time. According to Cleveland Clinic, some of the early signs are:

  • Diarrhea or urgent bowel movements
  • Abdominal (belly) cramping
  • Tiredness
  • Nausea
  • Weight loss (caused by lack of appetite) 
  • Anemia (reduced number of red blood cells)
  • Delayed growth and development in children

More advanced symptoms of ulcerative colitis include:

  • Blood, mucous, or pus in bowel movements
  • Rectal bleeding
  • Severe cramping
  • Fever
  • Skin rashes
  • Mouth sores
  • Joint pain
  • Red, painful eyes
  • Liver disease
  • Loss of fluids and nutrients
Symptoms of ulcerative colitis
Symptoms of ulcerative colitis. IBD Relief. Flickr.

In certain cases, ulcerative colitis may be linked to certain conditions that are outside of the digestive system such as arthritis, inflammation of the eye, liver disease and osteoporosis. These complications are thought to be a result of an overactive immune response associated with ulcerative colitis.

Causes of Ulcerative Colitis

Part 4 of Is ulcerative colitis genetic?

While the cause of ulcerative colitis is unknown, it is thought to be the combination of a number of factors including an immune system response, genetics, and the environment. 

Many doctors believe ulcerative colitis is an autoimmune disease in which the body’s immune system mistakenly attacks healthy cells in the digestive system. The result is the inflamed tissue in the affected area. There are a number of reasons being investigated as to the origin of the inflammation. 

One theory is that the body mistakes the good bacteria in the gut for dangerous bacteria while another theory suggests an outside bacterial infection that the immune system responds to but remains active after the infection clears. Others suggest that the immune system may simply malfunction on its own.  

Because the condition is more prevalent in certain areas of the world, there is thought to be a strong environmental factor in causing the disease. Namely, it is more common in developed countries in Northern Europe and North America. Some have suggested that air pollution, medication and certain diets may all play a role. Improved sanitation systems, and thus less bacteria exposure, may also contribute. 

Other ulcerative colitis risk factors include having a close family member with the disease, eating a high fat diet, or frequently using nonsteroidal anti-inflammatory drugs (NSAIDS) like ibuprofen (Advil® or Motrin®). Those of Ashkenazi Jewish descent are also at a higher risk of developing the condition. 

Diagnosis of Ulcerative Colitis

Part 6 of Is ulcerative colitis genetic?

The only way to positively diagnose ulcerative colitis is through a tissue biopsy. Other tests and procedures may be conducted to rule out similar conditions, such as Crohn’s disease. 

Lab tests

Blood tests for this condition normally look for signs of anemia, a lower than normal red blood cell count. Stool tests can also help diagnose the condition by analyzing for white blood cells in the stool or by ruling out other digestive conditions like bacteria or virus infections.

Endoscopic procedures

The most common method to diagnose this condition is through a colonoscopy. During this procedure, a thin, flexible, lighted tube with a camera on the end is weaved through the entire colon. A small amount of tissue for a biopsy is taken at this time. The biopsy is necessarily for a conclusive diagnosis. If the colon is very inflamed, an alternative procedure called a flexible sigmoidoscopy may be used instead. In this very similar procedure, the doctor will only insert the tube into the rectum and lower end of the colon.

A colonscopy procedure
A colonoscopy procedure. Wikipedia. CC-Attribution-Share Alike 4.0 International.

Imaging

Imaging techniques are only used if your doctor suspects serious complications from the disease. X-rays or CT scans can reveal serious damage, such as a perforated colon. Enterography scans are more sensitive tests that can identify inflammation through non-invasive procedures, especially if the inflammation has spread to the small intestine.  

Did you know you can test for inflammation at home? Check out this review article on at home inflammation tests to learn more!

Treatment of Ulcerative Colitis

Part 7 of Is ulcerative colitis genetic?

There is no cure for the condition, but medications and lifestyle changes can help treat the symptoms and improve quality of life. Medications are generally prescribed based on the severity of the disease and often have to be tailored to the individual patient.

Anti-inflammatories

Anti-inflammatory drugs, 5-aminosalicylates or corticosteroids, are often the first type of drug prescribed. 5-aminosalicylates can be taken as by mouth or as an enema or suppository, depending on where the damage is in your colon. Corticosteroids are normally reserved for short term treatment of more severe cases as they may result in serious side effects.

Immunosuppressants

Immune system suppressors will decrease the effect of the entire immune system in an effort to reduce the inflammation that is causing the ulcerative colitis symptoms. They can be prescribed alone or as a combination. 

Mayo Clinic describes some of the most commonly used immunosuppressants:

Azathioprine (Azasan, Imuran) and mercaptopurine (Purinethol, Purixan) are the most commonly prescribed types of this drug. You will keep regular check ups with your doctor to check for side effects such as effects on the liver and pancreas. 

For patients with ulcerative colitis who don’t respond well to those medications, they may try and take cyclosporine (Gengraf, Neoral, Sandimmune). This drug cannot be used in the long term due to serious side effects. 

Finally, tofacitinib (Xeljanz) can be prescribed if other therapies do not work well. Recently, the FDA reported preliminary data showing an increased risk of serious heart-related problems and cancer from taking this drug. Patients currently taking it should consult their doctor.

Biologics

Biologics are special types of drugs that target proteins in the immune system. They are generally reserved for severe cases that do not respond well to any other treatment. They can either block certain proteins produced by the immune system or prevent inflammatory cells from getting to the site of inflammation.

Most patients will take additional over the counter medications that can help reduce symptoms of the condition. They can include anti-diarrheal medications, pain relievers, antispasmodics (to help with cramps), and iron supplements (to treat anemia).

Surgery

Surgery is usually an option for the most severe cases. During this procedure, a surgeon will remove the colon and rectum. This will usually involve the surgeon constructing a pouch from the end of your small intestine attached directly to your anus so that you can pass stools fairly normally. If this is not possible, the surgeon will create a permanent opening through which stool is passed into a bag.

Screening

People with ulcerative colitis or Crohn’s disease need to be especially careful to screen for colon cancer, which they are at an increased risk for due to their condition. Learn more about colon cancer genetic testing in our special hereditary cancer series.

You can learn more about diagnosis and treatment options from the American Society of Colon and Rectal Surgeons.

If you liked this article, you should check out our other posts in the Nebula Research Library!