Taken together, these results suggest a potential role for ZIP8 in intestinal inflammation, induced by IFNγ in the intestinal epithelial compartment, and that perturbations in negative regulation of NF-κB by ZIP8 A391T may contribute to CD pathogenesis.
The variant, rs13107325, is almost exclusive of European populations and is one of the most pleiotropic variants of the genome, being associated at genome-wide significant level with several additional traits, such as body mass index, Crohn's disease, blood pressure related-traits, and serum levels of manganese, N-terminal pro-B-type natriuretic peptide and HDL-cholesterol.
We identified an association between CD and a missense variant encoding alanine or threonine at position 391 in the zinc transporter solute carrier family 39, member 8 protein (SLC39A8 alanine 391 threonine, rs13107325) and replicated the association with CD in 2 replication cohorts (combined meta-analysis P = 5.55 × 10(-13)).