rs601338
mixedMag 6.5This is a stop gained variant in the FUT2 gene.
Key Literature Trait Associations
Norovirus Susceptibility
Individuals carrying the G allele (secretors) are highly susceptible to genogroup II.4 norovirus infection because functional FUT2 produces HBGA ligands on intestinal epithelium that norovirus uses for cell attachment. A systematic review and meta-analysis found secretors are approximately 9.9-fold more likely to be infected with GII.4 norovirus (OR 9.9, 95% CI 3.9–24.8) compared to non-secretors. A Ugandan longitudinal cohort confirmed strong associations between secretor status and GII antibody titers (p=3.1×10⁻⁵²). Notably, some norovirus genogroups (e.g., GI.6) may infect non-secretors, and in East Asian populations rs601338 alone does not predict susceptibility as well as rs1047781.
Rotavirus susceptibility
Secretor-positive individuals (rs601338 G allele carriers with functional FUT2) are highly susceptible to P[8]-type rotavirus, the dominant human rotavirus strain globally. The meta-analysis by Kambhampati et al. found secretors are 26.6-fold more susceptible to P[8] rotavirus infections. A Rwandan pediatric cohort (n=668) confirmed that non-secretors (AA homozygotes) had significantly lower rotavirus infection rates (5.3% vs. 13%; OR 0.39, p=0.019). P[6] and P[4] rotaviruses use different HBGA ligands and may infect non-secretors, partially explaining why non-secretor protection is strain-specific.
Vitamin B12 Levels
The rs601338 A allele (non-secretor) is consistently associated with reduced serum vitamin B12 at genome-wide significance across multiple large GWAS and populations. The mechanism involves impaired haptocorrin (HC) glycosylation — functional FUT2 normally adds fucose to HC, and non-secretors show reduced holoHC-bound B12 in circulation, though transcobalamin-bound B12 (the metabolically active fraction) is unaffected. The original GWAS by Hazra et al. identified the signal at p=6.92×10⁻¹⁵ in 4,763 Americans; the association has been replicated in European and South Asian cohorts. Because the B12 reduction is primarily in haptocorrin-bound (storage) B12, the clinical significance for functional B12 deficiency is debated.
Chronic pancreatitis
A 2025 GWAS in 20,040 European individuals identified rs601338 as significantly associated with chronic pancreatitis, with the non-secretor A allele (homozygous AA) conferring ~26% increased risk (OR 1.26, 95% CI 1.07–1.48, p<0.001). The effect was more pronounced in males (OR 1.33, p=0.006) and showed synergistic interaction with smoking. The proposed mechanism involves altered intra-pancreatic fat deposition in non-secretors due to disrupted mucin glycosylation in pancreatic ductal epithelium.
Diarrheal disease
Secretor children (rs601338 G allele) have higher rates of diarrheal illness in early life, particularly during the first year. A GWAS meta-analysis across multiple European birth cohorts (n=5,758 + 3,784 replication) identified rs601338 as the likely causal FUT2 variant driving increased diarrhea risk, with protective effects in A allele carriers. A prospective Norwegian/Swedish cohort (n=700) further showed secretor mothers and secretor children had materially elevated gastroenteritis rates (IRR 1.48–1.56, p<0.05), with gut microbiota differences in Bacteroides and Escherichia species.
Crohn's disease
The rs601338 A allele (non-secretor) is associated with a more favorable clinical course in Crohn's disease (CD), with non-secretor homozygotes showing higher rates of sustained clinical remission. In a 5-year follow-up study of 62 CD patients, rs601338 mutation was independently associated with favorable outcome (OR 3.4, 95% CI 1.3–8.7, p=0.01). This may reflect altered microbial ecology and reduced inflammatory ligand expression in non-secretors. However, evidence across populations is inconsistent: Belgian data suggested FUT2 variants modulate CD susceptibility, while Japanese data linked secretor status specifically with colonic-type CD.
Pancreatic intraductal papillary mucinous neoplasm
A 2025 GWAS in 68,931 individuals from the Mass General Brigham Biobank identified rs601338 as significantly associated with pancreatic intraductal papillary mucinous neoplasms (IPMNs) at genome-wide significance (p=1.06×10⁻⁸). Although the reported OR of ~1.01 suggests a modest per-allele effect, the statistical significance exceeds genome-wide thresholds with a very large sample. The proposed mechanism links non-secretor status to altered mucin synthesis and carcinoembryonic antigen regulation in pancreatic ductal cells, consistent with IPMNs being mucin-producing lesions.
▶GWAS Catalog Trait Associations (62)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (62)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶ClinVar annotation
Bombay phenotype; Familial Otitis Media; SECRETOR/NONSECRETOR POLYMORPHISM; Vitamin b12 plasma level quantitative trait locus 1 (B12QTL1)
View on ClinVar →▶Research that mentions this SNP (1)
▶Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis BAssociationN=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.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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