Functional Toll-Like Receptor (TLR)2 polymorphisms in the susceptibility to inflammatory bowel disease

Publication

Functional Toll-Like Receptor (TLR)2 polymorphisms in the susceptibility to inflammatory bowel disease

Journal Paper/Review - Apr 7, 2017

Török Helga Paula, Bellon Victor, Konrad Astrid, Lacher Martin, Tonenchi Laurian, Siebeck Matthias, Brand Stephan, De Toni Enrico Narciso

Citation

Török H, Bellon V, Konrad A, Lacher M, Tonenchi L, Siebeck M, Brand S, De Toni E. Functional Toll-Like Receptor (TLR)2 polymorphisms in the susceptibility to inflammatory bowel disease. PloS one 2017; 12:e0175180.

Type

Journal Paper/Review (English)

Journal

PloS one 2017; 12

Publication Date

Apr 7, 2017

Issn Electronic

1932-6203

Pages

e0175180

Brief description/objective

BACKGROUND
The recent genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) suggest significant genetic overlap with complex mycobacterial diseases like tuberculosis or leprosy. TLR variants have previously been linked to susceptibility for mycobacterial diseases. Here we investigated the contribution to IBD risk of two TLR2 polymorphisms, the low-prevalence variant Arg753Gln and the GTn microsatellite repeat polymorphism in intron 2. We studied association with disease, possible correlations with phenotype and gene-gene interactions.

METHODOLOGY/PRINCIPAL FINDINGS
We conducted a large study in 843 patients with Crohn's disease, 426 patients with ulcerative colitis and 805 healthy, unrelated controls, all of European origin. Overall, the frequency for carriers of shorter GTn repeats in intron 2 of the TLR2 gene, which have previously been associated with low TLR2 expression and high IL-10 production, was slightly elevated in Crohn's disease and ulcerative colitis compared to healthy controls (16.0% resp. 16.7% vs. 12.8%). The highest frequency of short GTn carriers was noted among IBD patients on anti TNF-alpha therapy. However, none of these differences was significant in the multivariate analysis. The Arg753Gln polymorphism showed no association with any clinical subtype of IBD, including extensive colitis, for which such an association was previously described. We found no association with specific phenotypic disease subgroups. Also, epistasis analysis revealed no significant interactions between the two TLR2 variants and confirmed IBD susceptibility genes.

CONCLUSIONS
The two functional relevant polymorphisms in TLR2, the GTn microsatellite repeat polymorphism in intron 2 and the Arg753Gln variant do not seem to play a role in the susceptibility to Crohn's disease or ulcerative colitis.