rs602662

mixedMag 4.5

This is a variant in the FUT2 gene that changes a glycine to an serine.

Key Literature Trait Associations

Vitamin B12 Levels

Variant in FUT2 (secretor gene) that affects intestinal vitamin B12 absorption. The A allele reduces fucosyltransferase 2 activity, altering gut mucosa glycosylation and intrinsic factor binding. Non-secretors (homozygous A/A) tend to have lower B12 levels and may benefit from B12 supplementation monitoring.

Grarup N et al. “Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets.” Plos Genetics 9(6):e1003530 (2013)

Allele A

OR —

p 1.0e-20

N 45,576

Large GWAS

European (Icelandic, Danish)

Lu Y et al. “Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations.” Journal of Lipid Research 49(12):2582-2589 (2008)

Allele A

OR —

β -0.120

p 3.0e-16

Large GWAS

Hazra A et al. “Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway.” Human Molecular Genetics (2009)

Allele A

OR —

p 1.8e-15

N 4,763

Large GWAS

European (American)

Nongmaithem SS et al. “GWAS identifies population-specific new regulatory variants in FUT6 associated with plasma B12 concentrations in Indians.” Human Molecular Genetics 26(13):2551-2564 (2017)

Allele A

OR —

p 5.0e-8

N 4,419

Small GWAS

South Asian (Indian)

Tanaka T et al. “Genome-wide association study of vitamin B6, vitamin B12, folate, and homocysteine blood concentrations.” American Journal of Human Genetics 84(4):477-82 (2009)

Allele A

OR —

β 49.770

p 2.8e-20

N 3,617

Large GWAS

European (Italian)

Tanwar VS et al. “Common variant in FUT2 gene is associated with levels of vitamin B(12) in Indian population.” Gene (2013)

Allele A

OR —

p 1.0e-4

N 1,146

Preliminary work

South Asian (Indian)

Crohn's disease

The G allele of rs602662 (tagging FUT2 non-secretor status) is associated with increased susceptibility to Crohn's disease, reaching genome-wide significance in a combined discovery and replication analysis. Non-secretors lack fucosylated glycans on the intestinal mucosa, which alters microbial colonisation patterns and may disrupt the protective mucus barrier, thereby promoting inflammatory bowel pathology. The association was not replicated for ulcerative colitis, suggesting specificity to Crohn's disease. A subsequent IBD proteomics study found rs602662 acts as a trans-pQTL affecting plasma CCL25 and is associated with reduced faecal butyrate-producing bacteria, providing mechanistic plausibility.

McGovern DP et al. “Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease.” Human Molecular Genetics 19(17):3468-76 (2010)

Allele G

OR —

p 4.9e-8

N 5,631

Large GWAS

European (Caucasian)

Bourgonje AR et al. “The Effect of Phenotype and Genotype on the Plasma Proteome in Patients with Inflammatory Bowel Disease.” Journal of Crohn's & Colitis (2022)

Allele G

OR —

p —

N 1,176

Preliminary work

European

Gastrointestinal illness susceptibility

The G allele of rs602662 (non-secretor tag) is associated with higher rates of diarrhoeal illness in infants, consistent with the established role of FUT2-determined surface glycans in susceptibility to enteric pathogens including norovirus and rotavirus. In a birth cohort of 1,831 infants, rs602662 showed associations with gastrointestinal illness (ages 12–24 months, RR=1.41, p=1.7×10⁻⁷) and lower respiratory illness comparable to those reported for rs601338, with which it is in very high LD (r²=0.92). A separate GWAS meta-analysis identified the FUT2 locus as genome-wide significant for diarrhoea in young children.

Barton SJ et al. “FUT2 Genetic Variants and Reported Respiratory and Gastrointestinal Illnesses During Infancy.” The Journal of Infectious Diseases (2019)

Allele G

OR —

p 1.7e-7

N 1,831

Small GWAS

European (British)

Bustamante M et al. “A genome-wide association meta-analysis of diarrhoeal disease in young children identifies FUT2 locus and provides plausible biological pathways.” Human Molecular Genetics 25(18):4127-4142 (2016)

Allele G

OR —

p 5.0e-8

Meta-analysis

multi-ancestry

Primary sclerosing cholangitis

The FUT2 locus represented by rs602662 showed suggestive association with primary sclerosing cholangitis (PSC) in an international GWAS meta-analysis of 1,936 PSC cases and 6,470 controls (p=1.9×10⁻⁶), falling short of genome-wide significance. The authors proposed that non-secretor FUT2 status may alter biliary microbial composition, contributing to the bile duct inflammation characteristic of PSC. This finding requires replication in larger PSC cohorts before clinical significance can be established.

Folseraas T et al. “Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci.” Journal of Hepatology (2012)

Allele G

OR —

p 1.9e-6

N 8,406

Small GWAS

multi-ancestry (European-predominant)

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GWAS Catalog Trait Associations (28)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

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ClinVar annotation

confers_sensitivity

2 submitters1 publication

Familial Otitis Media; Levothyroxine response

View on ClinVar →

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Research that mentions this SNP (1)

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Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B

AssociationN=6,033Jiang DK et al.(2015)· Hepatology

A genome-wide association study of 83 plasma proteins relevant to cardiovascular disease in 3,394 European subjects identified 79 genome-wide significant loci (p<5e-8), with 55 replicating in independent cohorts (n=2,639). Using eQTL analysis and network methods, the authors proposed plausible causal mechanisms for 25 trans-acting loci including post-translational regulation of KITLG by MMP9 and several receptor-ligand pairs. Multiple loci showed evidence of causal association with coronary artery disease risk.

Traits studied:AtherosclerosisCoronary artery diseasePlaque rupturePlasma protein levels (83 cardiovascular disease-related proteins)Thrombosis

rs602662

Key Literature Trait Associations

Vitamin B12 Levels

Crohn's disease

Gastrointestinal illness susceptibility

Primary sclerosing cholangitis

GWAS Catalog Trait Associations (28)

ClinVar annotation

Research that mentions this SNP (1)

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