Inflammatory Genes Increase Risk of IBD

Inflammatory Genes Increase Risk of IBD

A new Danish study investigating the genetics behind inflammatory bowel disease (IBD) found that variants of inflammatory genes TLR1 and IL12B are associated with an increased risk of developing the disease. The team also found that a variant of the IL18 gene was associated with a lower risk of IBD.

The study, named Polymorphisms in the Toll-Like Receptor and the IL-23/IL-17 Pathways Were Associated with Susceptibility to Inflammatory Bowel Disease in a Danish Cohort, was performed by Steffen Bank and colleagues from Viborg Regional Hospital, Denmark in collaboration with a large number of Danish clinics and institutions. The article was published in the journal PLOS ONE in December 2015.

Enrolling 624 patients with Crohn’s disease (CD), 411 with ulcerative colitis (UC), and 795 controls, the team employed what is known as a candidate gene approach. Genes that are theoretically involved in a disease are screened for mutations (often using known mutations present in databases), and the team then explores if the gene variants are found more often in patients than in controls.

The team reported that when they looked separately at the different patient groups, they could see that variants of the inflammatory genes TLR1, TLR5, and IL12B were associated with an increased risk of CD, while in the UC group they only observed an association with TLR1. In both groups, the team found that IL18 was associated with a decreased risk.

When researchers combined the groups, comparing all IBD patients to controls, they still found that patients carrying variants of TLR1 and IL12 had an increased risk of IBD, while the IL18 variant posed a lower risk of developing the disease. However, employing a more rigid statistical approach accounting for the fact that numerous genes were tested at the same time, only the TLR1 variant was found increased in the patient group.

An association between a gene variant and a multifactorial disorder such as IBD does by no means signify that a carrier of that gene variant will definitely develop the disease. It is a mere indication that this gene, in combination with other genes and the environment, makes an individual more prone to develop IBD, compared to non-carriers.

The results of the study confirmed earlier findings of associations between IL12B and IBD. IL12B is a component of two other inflammatory signaling molecules – part of what is known as the IL23/IL17 pathway. On the other hand, the variant of the TLR1 gene investigated in the study had not been previously associated with an increased IBD risk.

The inflammatory genes investigated are involved in the response to ‘PAMPS’ – molecular patterns on the surface of bacteria and virus that signals infection, triggering an immune response in the host. The gene variants found in the study to be associated with an increased IBD risk cause a stronger immune reaction when the immune system is triggered.

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