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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Allele frequencies for the GTn repeat microsatellite polymorphism in the study groups.
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pone.0175180.g001: Allele frequencies for the GTn repeat microsatellite polymorphism in the study groups.

Mentions: The number of GT repeats in intron 2 of the TLR2 gene varied between 13 and 28 in both the disease groups and the healthy controls (see Fig 1). The polymorphic information content for the GTn repeat microsatellite polymorphism was 0.833, which can be considered highly informative.


Functional Toll-Like Receptor (TLR)2 polymorphisms in the susceptibility to inflammatory bowel disease
Allele frequencies for the GTn repeat microsatellite polymorphism in the study groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384663&req=5

pone.0175180.g001: Allele frequencies for the GTn repeat microsatellite polymorphism in the study groups.
Mentions: The number of GT repeats in intron 2 of the TLR2 gene varied between 13 and 28 in both the disease groups and the healthy controls (see Fig 1). The polymorphic information content for the GTn repeat microsatellite polymorphism was 0.833, which can be considered highly informative.

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.