Researchers have identified a gene that is linked to long-term
disease outcome in Crohn's disease, a common inflammatory bowel
disorder, and rheumatoid arthritis. The findings reveal targets
that could be exploited for new treatments.
The gene is involved in inflammation and is not associated with
the overall risk of developing disease, but patients with one
particular variant experienced better clinical outcomes.
Genetic studies have contributed greatly to our understanding of
susceptibility to complex diseases and the biological processes
that drive the development of disease. However, understanding the
factors that shape the course of a disease once it has developed is
equally important for ensuring patients have access to appropriate
treatments.
The international team, led by researchers at the Cambridge
Institute for Medical Research at the University of Cambridge,
looked at existing data from genome-wide association studies in
Crohn's disease to focus on prognosis rather than diagnosis. They
identified a variant in the FOXO3A gene that is associated with the
outcome of Crohn's disease but not associated with its
diagnosis.
By studying the effects of this particular gene variant on cells
cultured in the lab, they found that it blocks the production of
inflammatory chemicals, known as cytokines, that are known to be
responsible for aggravating disease symptoms in Crohn's disease and
other inflammatory diseases.
When the team looked at patients with another inflammatory
disease, rheumatoid arthritis, they found that the same gene
variant was linked to less joint damage over time, but not with
susceptibility to developing the disease in the first place.
The study also looked at patients with malaria in Kenya and
Vietnam, a disease in which inflammatory cytokines have a positive
rather than negative impact on disease outcome and are an important
part of the immune response to the initial infection. The findings
reveal that the same gene variant is linked with a greater
susceptibility to severe malaria.
Professor Ken Smith from the Cambridge Institute for Medical
Research said: "Our findings have important implications for how we
think about the biology of complex disease and, in particular, show
that genetic variants might control pathways that drive the
clinical outcome of disease without being associated with its
diagnosis. These pathways, which may influence multiple diseases,
may provide new targets for therapy to alter disease course."
The paper, Human
SNP links differential outcomes in inflammatory and infectious
disease to a FOXO3-regulated pathway, is published inCell.