Rs281408

A genome-wide association study of metabolic traits found that variations in rs281408 are strongly correlated with fucose levels in urine samples, which in turn are associated with inflammatory bowel disease and Crohn’s disease. This single nucleotide polymorphism is specifically found in the RASIP1 gene, with reference allele C and minor allele A (P = 9.5x10-27). RASIP1 is positioned within a large linkage-desequilibrium-block on chromosome 19 also encompassing FUT2 and IZUMO1. As such, rs281408 has a strong LD with rs492602 (r2 = 0.87), which is located within the FUT2 gene that encodes for fucosyltransferase.

FUT2 has previously been associated with vitamin B12 levels in the serum. The FUT2 gene product is integral for secretion and display of ABO blood group antigens on mucosal surface cells, which serve as a point of interaction with gut bacteria and pathogenic viruses. Furthermore, fucose levels (the substrate molecule of fucosyl treansferase) have been associated with gut health (by virtue of the microbial composition within) and, by extension, with inflammatory bowel disease and Crohn’s Disease. Indeed, Crohn’s Disease mouse models display increased urine fucose levels.