Some families seem to have more than their fair share of illness, especially in families with a propensity for autoimmune diseases, conditions that turn the body’s own infection-fighting cells against it, like type 1 diabetes and celiac disease.
These two autoimmune diseases often cluster together in families, and even in individuals. The prevalence of celiac disease in people with type 1 diabetes is five to 10 times higher than in the general population.
A report published this week by the New England Journal of Medicine shows that shared genetic risk factors are at least partially to blame. According to experts, these findings could help scientists understand more about the underlying biology of both diseases.
The researchers, led by Professor John Todd from the University of Cambridge, tested nine SNPs known to be associated with celiac disease in 8,064 type 1 diabetes patients, 9,339 controls, and 2,828 families with a child affected by the disease.
Four SNPs showed a significant association with type 1 diabetes. Three of these were novel findings. The association of a SNP in the SH2B3 gene with both diseases was already known from previous work.
When the researchers looked in the other direction, testing 19 SNPs known to be associated with type 1 diabetes in 2,560 people with celiac disease and the same 9,339 controls, two significant associations with celiac disease were found.
The total number of cross-acting SNPs was brought to seven when the researchers found that a variation called CCR5delta32 is also associated with the risk of developing both type 1 diabetes and celiac disease. CCR5delta32 is most famously associated with resistance to HIV infection.
Of the variants associated with both type 1 diabetes and celiac disease in this report, all but two had an effect in the same direction — the riskier version for one disease was also riskier for the other.
But the SNPs in IL18RAP and TAGAP had opposite effects. The T version of each SNP increased the risk for celiac disease, but decreased the risk for type 1 diabetes.
A SNP having a different effect on the risk for different diseases is not unheard of. The A version of in PTNP22 increases the risk of type 1 diabetes and rheumatoid arthritis, but has shown to be protective for Crohn’s.
In an accompanying editorial in NEJM, Dr. Robert Plenge suggests that the SNPs identified in this study could theoretically be used to screen patients with one disease (i.e. celiac) to predict their risk of developing the other (i.e. type 1 diabetes). This type of screening, however, is controversial. Plenge also notes that because each SNP contributes only a small increase in risk, their use would not be likely to add much utility to current screening measures.
“The most important implication [of this kind of research] is likely to be the ability to define biologic pathways, many of which are unexpected, that cause disease. Over many years, such insight may lead to the development of novel therapies to treat, prevent, or even cure disease,” Plenge wrote.