What's in Your Genes?

Student guest post by Liz Stepniak

In the field of chronic disease, genetics has long been determined as a component of disease susceptibility. Infectious disease was believed to be caused by an agent of infection, such as a virus or bacteria which comprises a large environmental factor. In the past decade or so, this view has been expanded to include an important genetic factor as well.

There has been scientific evidence supporting the controversial idea that one error in a single gene can significantly alter the individual's risk of obtaining a bacterial infection. Can infectious disease develop as a result of such genetic vulnerabilities? This idea was met with resistance from the microbiology field, which stresses that infectious diseases are strictly environmental. Immunologists have also viewed this idea with skepticism; since adding this component opens a large area of re-exploration for the possibilities of interactions between a range of microbes and certain immunological molecules. The positive implications of further research in this area is that it allows for a more complete and accurate way of treating infection. This also opens the door to further explanation of the immune system as a target for treatment instead of just the bacteria causing the infection.

There are many important components of infectious disease, but I'm going to focus on disease severity for the research I'm going to discuss further. This is by no means an exhaustive commentary, merely a discussion of a few papers I found interesting while I was looking into this topic and what it could bring to the scientific and medical worlds:
A study published in December 2008 took the first look into genetic determinants of severity of acute infectious illnesses. These researchers found that high-risk gene combinations made certain individuals 8 times more likely to suffer from a severe and prolonged illness. Another interesting result from this paper was that the converse was also true, a certain gene combination acted protectively; with these individuals having a less severe, shorter illness. I thought this was an interesting paper because in the future, it may be possible to identify those individuals at high-risk and provide prevention and more appropriate treatment for common infectious disease.

Recent research findings from Rockefeller University and the Necker Medical School that supports this idea has identified a new gene mutation that causes children to be more susceptible to mycobacterial diseases. Mycobacterium infection can lead to diseases like leprosy or tuberculosis. This January 2010 paper suggested that this mutation disrupts IFN- γR1, which is responsible for making a receptor for interferon γ, a molecule that leads the immune cells to form an attack on a foreign organism. It has been found that when this receptor is absent or not fully functional, an immune system pathway that specifically targets mycobacterium is disrupted. This was a small study, only done in 118 patients with complete or partial IFN-γR1 deficiency; but 33 different IFN-γR1 mutations were found among these patients.

A researcher conducting this study explained that the severity of the disease depended on the severity of the deficiency, and that for this deficiency; there was little difference between partial and complete deficiency leading to a dramatic increase in the severity of the mycobacterial disease. For one young patient, the researchers sequenced the genes of this patient and her healthy family members. They found that each parent had one copy of the mutation located on the initiation codon. This article also provided further evidence to the idea that an error in a single gene may be enough to radically alter individual risk for bacterial disease. This research group, led by Jean Laurent Casanova has also conducted research studies showing underlying genetic vulnerabilities to other infectious diseases including pneumococcal disease and herpes simplex encephalitis.

I found this topic interesting because a lot of important efforts focus on altering environmental factors that cause disease but the strong presence of a genetic component just keeps sneaking into all forms of disease and illness and adding a complexity to understanding and treatment. It just goes to show how interactive the battle between the human body and infectious agents has become! While there have been multiple studies demonstrating the important role of genetics in infectious disease, there is further evidence needed to better understand the multifaceted puzzle that results from the interactions of genetics, environments, and infectious agents with regards to all disease components. As with most research, the more discoveries investigators make, the more it makes us realize is still out there to be uncovered and understood. Even though this may add to the difficulty of understanding infectious diseases; with more research in this area, the outcome can lead to better treatments and prevention efforts of infectious diseases and more lives saved.

Works Cited:

Kong et al. (2010). A novel form of cell type-specific partial IFN-γR1 deficiency caused by a germ line mutation of the IFNGR1 initiation codon. Human Molecular Genetics, 19 (3): 434-444

Rockefeller University (2010, February 21). Human genetic vulnerabilities may underlie infectious diseases, scientist argues. ScienceDaily

Rockefeller University (2010, January 1). Mutation leads to new and severe form of bacterial disease. ScienceDaily.

University of New South Wales (2008, December 9). Blame Your Genes: Some People Eight Times More Likely To Suffer From Prolonged Illness With Infection. ScienceDaily.