Possible Inherited (Genetic) Factors Of IBD

Crohn's disease and ulcerative colitis have a tendency to run in families. This inherited susceptibility to the disease is carried within the genetic code. The genetic code is present, at some point in development, in every cell of the human body and is passed down from parent to child. Recent research has shown that there are likely at least three and probably several more inherited susceptibility factors (genes) that, when altered, can increase a person's chances of developing IBD.

 

 

In studies of twins, in which at least one twin has IBD, it has been found that if one twin has Crohn's disease, the likelihood that the other twin also has Crohn's disease is much higher if the twins are genetically identical than if the twins are not genetically identical (fraternal twins). Since both identical twins and fraternal twins tend to share the same non-inherited factors, such as diet and environmental exposures, the higher risk in identical twins means that a genetic or inherited factor must be playing an important role in causing disease susceptibility.

 

 

By examining the patterns of IBD inheritance in families, it is clear that Crohn's disease and ulcerative colitis are not passed from parent to child in a simple or direct fashion the way that some physical characteristics, such as eye color, blood type, or some diseases (cystic fibrosis, for example) are passed on from parent to child. In those instances, a single gene is responsible for the particular characteristic or disease. In IBD, it appears that mutations of multiple genes are required to produce increased susceptibility to the disease.

 

Research into the genetic factors that contribute to IBD has been exploding in the past decade with several major successes. These successes will almost certainly lead to improved understanding of how IBD occurs and, with time, may lead to improved treatments or preventive therapy.

 

 

If you or a family member has IBD, the fact that certain genes, when abnormal, may lead to an increased risk of developing IBD is of some interest, particularly if such knowledge ultimately leads to more effective treatment, prevention, or even cure. However, what you really want to know is what is the risk to other family members and is there a way to predict who might develop IBD?

 

The risk of developing IBD is highest in first-degree relatives (brothers, sisters, parents, and children) of an affected individual. This risk to family members is higher if the person has Crohn's disease rather than ulcerative colitis. The risks described below are estimated based upon the observed frequency of Crohn's disease and ulcerative colitis within families and should not be considered to necessarily be exact.

 

 

Unfortunately, genetic testing for IBD is not yet sensitive enough to be used as a routine tool to predict the development of disease. Even if predictive tests were more sensitive, the results may not be valuable for treating the disease for several reasons.

 

 

A positive genetic test in someone with a family history may make that person or family members more vigilant in watching for early signs of disease. This may unnecessarily increase anxiety around the occurrence of symptoms that are in no way related to IBD.

 

 

We also do not know if earlier detection of disease, even before symptoms have begun, will allow more effective treatment of acute symptoms or prevention of long-term disease complications. Early treatment of the disease, before symptoms have begun, may produce more harm than good, unless that treatment is highly effective and very safe. Current treatments for IBD are either minimally effective or are more effective but with the cost of potential side effects, some of which may be quite serious. Despite the reservations surrounding genetic testing, it is quite likely that some people with a family history of IBD and even some without any family history will wish to have genetic testing where it is made available. Although we do not know for certain if early treatment is of benefit, many people with positive genetic tests, even without signs or symptoms of disease, will choose to receive treatment. In a survey of IBD patients, a large percentage said they would choose to have genetic testing for their children, even if a positive test had a very low likelihood of predicting disease.

 

 

Where genetic testing may be more widely used, at least in the next 5 to 10 years, is for predicting complications of the disease and predicting the course of the disease. Genetic testing may also prove to be valuable in treating the disease, especially in choosing effective medications. This involves the science of pharmacogenomics.

 

Pharmacogenomics is the use of genetic testing to predict various aspects of response — both good and bad — to medications. For example, genetic testing may predict who will respond positively to a given medication and who will likely develop side effects and thus may not be a good candidate for a given medication or may require closer monitoring.

 

In IBD treatment, this may occur with the use of the immune modulator drugs, azathioprine and 6-mercaptopurine. The way these drugs are metabolized (broken down) in the body is determined, to a large extent, by genetic factors. Most people break the drug down into inactive by-products at roughly the same rate. However, about 10% of people break the drug down slightly more slowly, and about 1% or less break the drug down very slowly. With slow drug metabolism, there may be higher levels of the active drug in the body for the same dose. Levels of the drug that are too high tend to produce toxicity to the bone marrow, resulting in production of fewer white blood cells and the possibility of infection.

 

Metabolism of these drugs is determined by the level of the TPMT enzyme in the bloodstream, which, in turn, is determined, to a large extent, by a specific genetic factor that can be detected through blood tests. By testing for the level of this enzyme in the blood, it may be possible to predict who is at risk for complications that occur as a result of high drug levels in the body.