Biochesmistry

A genetic test for cardiovascular diseases

A genetic test that currently helps physicians gauge the compatibility of donated organs and their recipients is helping to measure the risks of being struck with such widespread conditions as cardiovascular disease and rheumatoid arthritis.

The test, known as human leukocyte antigen (HLA) typing, is performed for kidney, bone marrow, liver, pancreas, and heart transplants. It’s a means of matching HLA antigens, which boost the body’s ability to fight infection. The probability that a transplant will be successful increases with the number of identical HLA antigen matches.

It’s this information that leads John Rioux, a professor in UdeM’s Faculty of Medicine, to build a model of inconceivable complexity. Where the airplane model maker would be using plastic and glue, Dr. Rioux’s materials are more elusive, employing genes with functions still mostly unknown, though six of them are at least known for their functions in the well-established organ compatibility test, and myriad disease mechanisms yet to be matched.

But that kind of complex calculation is the stock in trade of the researcher, who holds the Canada Research Chair in Genetics and Genomic Medicine of Inflammation. In 2001, he and his former team members at the prestigious Whitehead/ Massachusetts Institute of Technology Center for Genome Research designed a framework that made gene hunting a lot more efficient. It provided the impetus for building a “haplotype” map of the genome, reducing the complexity from hundreds and thousands of combinations of genetic variants to a very few limited "flavours" of each gene.  His team was then able to use this knowledge to design a novel approach in the search for a susceptibility gene for Crohn's disease.

The particular model he’s now working on would also have major implications, helping to predict the likelihood of being diagnosed with a variety of inflammatory diseases, not only rheumatoid arthritis and cardiovascular disease, but also Crohn’s disease and lupus. Inflammatory diseases are a group of medical ailments that have been set off by an immune system gone awry. Whereas our immune system is supposed to protect us from disease, in people with immune-mediated conditions, the immune system has begun attacking the body with various symptoms, in this case inflammation.

On a genetic level, cardiovascular and Crohn’s disease, rheumatoid arthritis and lupus all have a few things in common. Not only are they all immune-mediated conditions but they also share the same 100-gene region of the genome, an area that also counts the six genes from the organ-recipient test. Dr. Rioux says it’s that sharing of the immune-related region of the genome that will help in putting together a risk assessment. “These genes have a role to play in the immune system. It makes them plausible candidates for immune-mediated conditions,” says the Canadian-born researcher, who up until he joined UdeM last year had been working in the US since his post-doctoral studies.

Dr. Rioux says his role is to look at the relationship between all the variants of these inflammatory diseases, come up with the risks of getting the disease and hopefully find ways to bring down those risks. He tries to identify the paths our biology takes in making us susceptible to certain diseases. That warehouse of knowledge will help in leading other researchers to eventual drug therapies, improved diagnoses or better clinical management of individuals with inflammatory diseases.