rs601338

Chromosome 19
Position 49206673
Gene FUT2

AA (TT)

50.250.2%

AG (TC)

35.335.3%

GG (CC)

14.514.5%

The A (T) allele is associated with: 

  • AA (TT) may have a genetic immunity to infection by the Norwalk norovirus, a cause of gastroenteritis (Ref).
  • AA (TT) leads to the absence of ABH blood groups in body fluids (Ref).
  • AA (TT) increases the risk of developing Celiacs by 1.28X (P=0.0074) (Ref).
  • The A (T) allele showed some protection from Ulcerative Colitis and Crohn’s Disease (P=0.035, OR: 0.84) (Ref).
  • AA genotype carriers may see slightly elevated values for B12 levels in their serum but this may not be necessarily reflective of their functional B12 levels in cells PMID: 19744961, PMID: 29040465. AG genotype likely have normal levels of serum B12

The G (C) allele is associated with:

  • Possible increased risk of developing Irritable Bowel Syndrome (IBD) in the Finnish population (Ref).
  • Higher levels of Bifidobacteria in the body (Ref).
Research Studies:
  1. The FUT2 secretor variant p.Trp154Ter influences serum vitamin B12 concentration via holo-haptocorrin, but not holo-transcobalamin, and is associated with haptocorrin glycosylation.
  2. FUT2 non-secretor status is associated with altered susceptibility to symptomatic enterotoxigenic Escherichia coli infection in Bangladeshis.
  3. FUT2 genetic variants as predictors of tumor development with hepatocellular carcinoma.
  4. Association of combined GIF290T>C heterozygous mutation/FUT2 secretor variant with neural tube defects.
  5. GWAS identifies population-specific new regulatory variants in FUT6 associated with plasma B12 concentrations in Indians.
  6. Population Structure of UK Biobank and Ancient Eurasians Reveals Adaptation at Genes Influencing Blood Pressure.
  7. A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways.
  8. A common genetic variant of fucosyltransferase 2 correlates with serum carcinoembryonic antigen levels and affects cancer screening in patients with primary sclerosing cholangitis.
  9. Association of Ulcerative Colitis with FUT2 and FUT3 Polymorphisms in Patients from Southeast China.
  10. Combinations of FUT2 gene polymorphisms and environmental factors are associated with oral cancer risk.
  11. Association of elevated rotavirus-specific antibody titers with HBGA secretor status in Swedish individuals: The FUT2 gene as a putative susceptibility determinant for infection.
  12. FUT 2 polymorphism and outcome in very-low-birth-weight infants.
  13. Personalized genetic testing and norovirus susceptibility.
  14. Faecal microbiota composition in adults is associated with the FUT2 gene determining the secretor status.
  15. Associations of FUT2 and FUT3 gene polymorphisms with Crohn’s disease in Chinese patients.
  16. Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis.
  17. FUT2: filling the gap between genes and environment in Behcet’s disease?
  18. Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant.
  19. Association study of FUT2 (rs601338) with celiac disease and inflammatory bowel disease in the Finnish population.
  20. Association of fucosyltransferase 2 gene variants with ulcerative colitis in Han and Uyghur patients in China.
  21. Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci.
  22. Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway.

EXPRESSION CONTROL


Decrease activity ↓
  • (+)-JQ1 compound (Ref)

Animal Studies:

  • Diethylnitrosamine (Ref)
  • Topotecan (Ref)
  • Bisphenol A (Ref)
  • Caffeic acid phenethyl ester (Ref)
  • Nickel monoxide (Ref)
  • Oxaliplatin (Ref)

Increase activity

Animal Studies:


Can work both ways


Clinical tips

Non-secretors have lower levels of bifidobacteria and would benefit from supplementing with Bifidobacteria strains of  probiotics. Rs601338, AA  (or TT) genotype are non-secretors and generally have significantly lower amounts of bifidobacteria.

Oligosaccharides are a carbohydrate that consists of three to nine monosaccharides (simple sugar).  There are three types of oligosaccharides that can be helpful prebiotics for people affected by the FUT2 gene: fructooligosaccharides (FOS), galactooligosaccharides (GOS), and inulin.  You can get oligosaccharides as prebiotic supplements and they are also found in foods like leeks, Jerusalem artichokes, onions, chicory root, and oats. If you suffer from SIBO however, these may be counterproductive.

Estrogen increases FUT2 expression (Ref).

FUT2 is involved in the formation of an immune complex, H antigen. FUT2 forms a sugar- polymer known as oligosaccharide (a few monosaccharides covalently linked), which then becomes “food” for gut flora. FUT2 regulates the expression of certain “blood-group antigens”,  and as such, directly influence bowel flora concentrations. Approximately twenty percent of the population has FUT2 gene mutations.

Carriers of the FUT2 genetic mutations have been shown to have lower concentrations of the gut microbe, bifidobacterium; a key beneficial microbial colony that lines the gut. Carriers of FUT2 genetic mutations confer a greater predisposition towards Crohn’s disease and elevated serum concentrations of vitamin B-12. These FUT2 “non-secretors” however appear to have a greater resistance towards certain pathogenic infections such as H Pylori, as well as protection against certain viruses, but there is conflicting data with the norovirus. So there are benefits and downsides  to being both: non secretor and secretor.

Homozygous FUT2 SNPs – Dietary adjustments may be important. Avoiding  grains, dairy, legumes, eggs, nuts, yeast, and soy can prove to be helpful, but there are exceptions to eliminating one or more food categories.

Check vitamin B6, magnesium, and zinc levels as they are depleted by higher oxalate foods. Unfortunately, they are found in some healthy leafy greens, sweet potatoes, and more. Great Plains OATs test can shed some light on whether an oxalate issue exists and whether the oxalate issue is gut yeast driven (and too much vitamin C consumption), genetically driven, or simply dietary driven (e.g., juicing greens daily) and individual is depleted of nutrients for oxalate-breakdown enzymes to do their job.(Ref)

Besides oxalates, lectins are another source of “anti-nutrients” used by the plant kingdom to protect themselves from predators. They also pose a problem for many with FUT2 SNPs.

Common polymorphisms in FUT2 define the vitamin B-12 plasma level. Vitamin B-12 is necessary for the formation of red blood cells, DNA synthesis during cell division, and maintenance of the myelin nerve sheath, among other functions.

FUT2 gene makes an enzyme that affects the sugars on our cells (glycoproteins).

People who have the AA genotype for rs601338 don’t show their blood type in their spit, mucus, or semen. This can change the bacteria in their gut and affect their vitamin B12 levels. Older studies suggested that people with this genetic code have higher levels of B12, but newer studies suggest that the B12 levels measured in their serum might not show how much is actually active in their body. So, if you have this genetic code, it’s not a good idea to rely on a blood test to check your B12 levels. Instead, testing for a substance called methylmalonic acid can give a better idea of your B12 status.

Approximately fifteen percent of the population have homozygous FUT2 rs1047781 and/or rs602662 polymorphisms and are referred to as, “non-secretors of H antigen in  East Asian population.  PMID: 8621666

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