A special diet, surgery or medication… which IBD treatment is right for you? Recent research studies say your genes will have the answer.
In fact, your genetics can help to explain a common phenomenon why people with IBD who get the same treatment get different results: some patients improve while others do not.
Based on clinical, radiologic and endoscopic findings, Inflammatory bowel disease (IBD) is traditionally classified as a group of disorders that involves chronic inflammation and can affect all or parts of your digestive tract. Crohn’s disease and ulcerative colitis are two major types of IBD, however about 10% of patients are known as having indeterminate colitis.
However, with help of recent genetic studies this traditional view is now being challenged. Scientists use DNA as a valuable tool that leads to an understanding that IBD is a group of complex conditions that have different clinical manifestations in terms of disease behavior, location and response to treatment.
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Want To Find The Right IBD Treatment? Look To Your Genes
The research shows that IBD runs in your family there is a strong genetic predisposition to acquire the disease. Up to 23% of individuals with Crohn’s disease and up to 16% of people with ulcerative colitis have family history of IBD. Based on the twins studies, first degree relatives are at the highest risk and have at least a 10-fold increased risk to develop it.
IBD involves a complex interaction between genetic and environmental factors that triggers an autoimmune response and results in chronic relapsing intestinal inflammation. There are periods when the disease becomes active and you experience severe inflammation of the digestive tract and flare-up of your symptoms. At the time when inflammation and symptoms subside IBD goes into a remission.
If you have IBD running in your family don’t feel as a helpless victim of your genetics and that there is nothing you can do to prevent or stop the progression of Crohn’s disease or Ulcerative Colitis.
In fact, the opposite is true – nowadays you can use your genetics to your advantage for IBD prevention and to achieve a better treatment outcome.
Today I’d like to share with you some new principal discoveries that have been made in IBD genetics in the last decade and explain how these can affect your IBD treatment already today.
Recent Advances In IBD Genetic Research
Over the past decades, there have been many discoveries that allowed a better understanding how genes contribute to IBD. These advances became possible due to new technologies in genetic testing, DNA analysis and use of large databases to complete new genome-wide association studies (GWAS) to identify single genes related to IBD.
Here is what we know today:
Multiple Genes Are Involved In IBD
Just recently IBD research studies have shown a tremendous success in the identification of disease susceptibility genes. Large GWAS of Crohn’s disease and ulcerative colitis have revolutionized the search for genetic loci associated with these complex diseases, dramatically increased our knowledge of IBD genetic risk factors and how many genes are involved.
While in 2001 only 3 genes associated with IBD had been identified, by 2011 the number of confirmed Chrohn’s disease susceptibility genes/loci increased to 71 and the number of known ulcerative colitis genes increased to 47.
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Only a year later in 2012, the International IBD Genetics Consortium (IIBDGC) performed one of the largest meta-analyses that was based on 75,000 IBD cases and controls including data from 15 different GWAS for both Crohn’s disease and ulcerative colitis. This study increased the total number of independent IBD risk loci to 163.
The principal insight learned from the IBD genetic studies was that there is no a single gene nor even a very small number but rather a large group of involved genes.
Shared And Unique Genetics In Crohn’s Disease And Ulcerative Colitis
Out of 163 IBD-risk genes 110 were identified to be related to both Crohn’s disease and ulcerative colitis, 30 are only Crohn’s disease specific and 23 genes are characteristic specifically for ulcerative colitis.
As you may see on the diagram below, some genes are shared by Crohn’s and ulcerative colitis while others are disease-specific. This suggests that nearly all biological mechanisms involved in one disease play some role in the other.
Loci associated with inflammatory bowel disease (IBD) are shown in black, Crohn’s disease (CD) in blue and ulcerative colitis (UC) in green. Source: Ann Gastroenterol. 2014;27(4):294-303.
Family-based studies on ulcerative colitis and Crohn’s disease have provided crucial findings about different genetic patterns of IBD and how much of the susceptibility to IBD is related to genetics.
About 75% of all families with patients who have a family history of IBD, show that the same disease either Crohn’s or ulcerative colitis appear through the generations while the remaining 25% of families have a mix of both conditions present.
These data correlate with findings of genetic studies and suggest that some genetic variants are disease specific and some variants are common to both Crohn’s disease and ulcerative colitis, whereby environmental factors might influence disease phenotype by “turning on” certain genes.
Some people with IBD cannot get a definitive diagnosis of Crohn’s or ulcerative colitis and has been traditionally categorized as having IBD unclassified. Genetic studies on familial IBD point out that there could be a genetic basis for the existence of more different subgroups and genetic phenotypes.
Genetic Indicators Of Autoimmunity, Inflammation And Increased Intestinal Permeability
It is important to note that a large amount of IBD risk genes are also shared with other health conditions related to immune system imbalances, mainly autoimmune disease and conditions that involve the immune system’s response to pathogens.
Initially, it was thought that IBD is an autoimmune condition where Crohn’s and ulcerative colitis were primarily TH1 and TH2 mediated diseases, respectively. However, recent genetic studies confirmed that some new discovered IBD-associated genes are involved in the maintenance of TH17 cells which coordinate our body’s defence against specific pathogens and mediate inflammation.
Other IBD-risk genes are involved in regulating the intestinal epithelial barrier and several physiological processes responsible for its maintenance such as assembly and regulation of tight junctions (space between cells building the intestinal wall), cell adhesion and polarity, mucus and glycoprotein regulation, bacterial sensing, gut health, membrane transport, epithelial cell growth and intestinal wall repair.
These new discoveries suggest that genetically susceptible individuals who are unable to clear invading pathogens and/or generate adequate immune tolerance to gut microbiota develop chronic, relapsing intestinal inflammation.
Another big discovery was that a large portion of IBD risk genes are shared with other autoimmune conditions and bacteria related diseases. The researchers found a strong overlap between IBD susceptibility genes and genes tied to the immune system’s response to mycobacterial infections including tuberculosis and leprosy.
IBD was found to be associated with other genetically determined syndromes including Turner syndrome, Hermansky-Pudlak syndrome, glycogen storage disease, cystic fibrosis and pachydermoperiostosis. An increased prevalence of IBD has also been observed in other complex diseases, especially those that have strong evidence of genetic predisposition and are driven by abnormal inflammation such as ankylosing spondylitis, psoriasis, multiple sclerosis and celiac disease.
According to researches:
“These findings open up tremendous avenues for targeted development of new therapies in IBD, but might also be relevant to understanding how treatment of one immune-mediated disease can trigger development of another”.
The Future Of IBD Genetic Studies
Despite a huge progress that was made in genetic studies during the last decade there are some questions that remain unanswered and are the subject of future research initiatives.
Current research findings only partially explain why IBD has such high heritability. Further studies of causative genes can help us better understand the underlying changes that lead to IBD. This could, in turn, be of potential great benefit in predicting the course of disease in individual patients and in establishing an appropriate genotype-specific treatment.
Knowing your DNA could allow the identification of family members at risk for developing IBD. Phenotypic similarities in families and twins suggest that genetics also influences the phenotype of the disease.
Discovery of new phenotypes or even phenotypic subcategories can bring more clarity in IBD classification and provide a better diagnosis of Crohn’s disease vs. Ulcerative Colitis, IBD unclassified and indeterminate colitis. By studying these individual subtypes, researches may be able to predict long-term clinical outcomes and make progress in identifying those individuals that should be targeted for early and/or aggressive clinical treatment.
Preliminary data also suggest that genetic analyses might be used for prediction of treatment response in the future. The IIBDGC’s study on the risk of colectomy in acute severe ulcerative colitis might be the most promising example, where an association between rs2403456 (11p15.3) and colectomy has been reported.
This brings us closer to personalized medicine where doctors will be treating IBD at the individual level and specifically tailor their recommendations rather than using a one-size-fits-all approach and hope that it works.
Your DNA has a purpose. It can help to understand not only why people get IBD but also what can be done for prevention, successful treatment and recovery.
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References:
1. The history of genetics in inflammatory bowel disease. Ann Gastroenterol. 2014;27(4):294-303.
2. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet. 2014 Nov;46(11):1187-96.
3. Genetics and innate and adaptive immunity in IBD. Nestle Nutr Inst Workshop Ser. 2014;79:41-55.
4. IBD candidate genes and intestinal barrier regulation. Inflamm Bowel Dis. 2014 Oct;20(10):1829-49.
5. Diet, microbes, and host genetics: the perfect storm in inflammatory bowel diseases. J Gastroenterol. 2013 Mar;48(3):315-21.
6. Clinical implications of inflammatory bowel disease genetics on phenotype. Inflamm Bowel Dis. 2005 Jan;11(1):56-61.
*Photo credit: Some images are courtesy of stockimages of samarttiw Ambro and dream designs from FreeDigitalPhotos.net
My name is Marina Gutner, PhD. I am a researcher, medical writer, Author of forthcoming series on thyroid, hypothyroidism and autoimmune disease. I was diagnosed with autoimmune Hashimoto’s disease and hypothyroidism in 2004 and soon got so sick that I was unable to function. It took me years of research to find how to recover from severe adrenal insufficiency, stop Hashimoto’s and reduce my high dose of thyroid medication. On my blog I show you exactly how I did it so you can learn how to get started. Read more in 
