Human intelectin-1 (ITLN1) genetic variation and intestinal expression

Abstract

Intelectins are ancient carbohydrate binding proteins, spanning chordate evolution and implicated in multiple human diseases. Previous GWAS have linked SNPs in ITLN1 (also known as omentin) with susceptibility to Crohn’s disease (CD); however, analysis of possible functional signifcance of SNPs at this locus is lacking. Using the Ensembl database, pairwise linkage disequilibrium (LD) analyses indicated that several disease-associated SNPs at the ITLN1 locus, including SNPs in CD244 and Ly9, were in LD. The alleles comprising the risk haplotype are the major alleles in European (67%), but minor alleles in African superpopulations. Neither ITLN1 mRNA nor protein abundance in intestinal tissue, which we confrm as goblet-cell derived, was altered in the CD samples overall nor when samples were analyzed according to genotype. Moreover, the missense variant V109D does not infuence ITLN1 glycan binding to the glycan β-D-galactofuranose or protein–protein oligomerization. Taken together, our data are an important step in defning the role(s) of the CD-risk haplotype by determining that risk is unlikely to be due to changes in ITLN1 carbohydrate recognition, protein oligomerization, or expression levels in intestinal mucosa. Our fndings suggest that the relationship between the genomic data and disease arises from changes in CD244 or Ly9 biology, diferences in ITLN1 expression in other tissues, or an alteration in ITLN1 interaction with other proteins.