What this means

FUT2 encodes the fucosyltransferase 2 enzyme, which adds a specific fucose sugar to glycoproteins on the apical surface of mucosal cells — most famously letting your ABO blood-group antigens appear on the gut lining and in saliva. The rs601338 A allele (W143X) is a nonsense mutation that abolishes enzyme activity. Homozygous A carriers are "non-secretors". Three things flow from that: (1) most clinical norovirus strains use H-type antigens as gut-cell receptors, so non- secretors are essentially resistant to them — one of the cleanest examples of a common genetic variant conferring infection resistance; (2) the gut mucus composition differs, producing measurable shifts in microbiome composition; (3) serum vitamin B12 levels are slightly lower on average. Heterozygous carriers are functionally secretors — one working copy makes enough enzyme.

FUT2 makes an enzyme that decorates the lining of your gut and other mucosal surfaces with the same sugar groups that define your ABO blood type. About a fifth of people of European ancestry carry two broken copies of this gene — these are "non-secretors". Their gut lining isn't decorated this way, with three knock-on effects: most norovirus strains can't latch on (you're broadly immune to "the winter vomiting bug"), the gut microbiome looks slightly different, and vitamin B12 levels run a touch lower on average. One working copy is enough — heterozygous carriers behave exactly like secretors.

Caveats

• Non-secretor status protects against most norovirus strains but not all — a few rarer strains can still infect non-secretors.
• The B12 effect is small; non-secretors generally have B12 levels in the normal range.
• Microbiome differences are real but their clinical importance is still being worked out.
• Some studies link FUT2 status to risk of Crohn's disease and to autoimmunity — the signal is small and not always replicated.

Populations

• Allele frequency for non-secretor status varies by ancestry; non-secretors are ~20% of Europeans, much rarer in some other populations

References

• Lindesmith et al. — Human susceptibility and resistance to Norwalk virus infection (Nature Medicine, 2003)
• Tong et al. — Reprograming of gut microbiome energy metabolism by the FUT2 Crohn's disease risk polymorphism (ISME Journal, 2014)
• Hazra et al. — Common variants of FUT2 are associated with plasma vitamin B12 levels (Nature Genetics, 2008)