Single nucleotide polymorphisms in C-type lectin genes, clustered in the IBD2 and IBD6 susceptibility loci, may play a role in the pathogenesis of inflammatory bowel diseases.

BACKGROUND AND AIM:The balance between microbes and host defence mechanisms at the mucosal frontier plays an important, yet unclarified role in the pathogenesis of inflammatory bowel disease (IBD). The importance of microorganisms in IBD is supported by the association of IBD with mutations in pattern recognition receptors (PRRs) such as NOD2 and TLR4. We aimed to examine whether polymorphisms in another type of PRRs, the so-called C-type lectin receptors (CLRs), are associated with IBD. Growing insights into the pathogenetic role of NOD2 mutations in Crohn's disease (CD) and the fact that the majority of CLR-encoding genes are located in IBD susceptibility loci provide strong arguments for further exploration of the role of CLRs in IBD. METHODS:In this study, we selected four single nucleotide polymorphisms (SNPs) in different CLRs to determine whether there could be a role for these CLRs in IBD. Functional SNPs in the genes coding for the candidate CLRs DC-SIGN, LLT1, DCIR and MGL were examined. Genotyping of all SNPs was performed at the Academic Medical Center. In this study, around 1572 samples were included from a maximum of 621 CD patients, 457 ulcerative colitis (UC) patients and 586 healthy controls (HCs). RESULTS AND CONCLUSION:No association was found between our IBD cohort and the candidate SNPs for DC-SIGN (CD/HC: P=0.25 and UC/HC: P=0.36), DCIR (CD/HC: P=0.22 and UC/HC: P=0.41) and MGL (CD/HC: P=0.37 and UC/HC: P=0.25). However, one polymorphism in LLT1 was found to be associated with our CD population (P<0.034). Our UC cohort was not associated with the variation in LLT1 (P=0.33). LLT1 is a ligand for the recently discovered CD161. CD161 is a new surface marker for human interleukin (IL)-17-producing Th17 cells. The Th17 phenotype has been linked to CD by the fact that IL-22, IL-17 and IL-23 receptor levels are increased in CD. The signal transduction pathways involving LLT1 and CD161 are not completely clarified and are currently under investigation in our laboratory.

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