Vitamin B12 (FUT2, CUBN, TCN2)

FUT2 · CUBN · TCN2

The blood vitamin B12 level is strongly heritable. Three genes explain a substantial part: FUT2 (secretor status and microbiota), CUBN (uptake in the gut) and TCN2 (transport in blood). They act together and explain why some people have lower values on the same diet.

The markers

FUT2 (rs602662, in strong linkage disequilibrium with the non-secretor mutation W143X) alters the B12 level via the gastrointestinal mucosa and the microbiota; in genome-wide studies this region was the strongest locus for plasma B12 (p ≈ 10⁻¹⁵ to 10⁻¹⁷; Hazra 2008, Hazra 2009). Cubilin (CUBN, rs1801222) mediates intrinsic-factor-B12 uptake in the ileum; the CUBN region was co-confirmed in the B12 meta-analysis. Transcobalamin II (TCN2, rs11254363) transports B12 in the blood to cells and alters transport capacity.

What it means

Together these markers explain part of individual B12 levels and the response to intake. It matters to separate total B12 from functional B12: holotranscobalamin and methylmalonic acid show the actual status better than the total. A genetically explainable low value is not automatically a deficiency, but it can explain why someone reaches the limit sooner. Secretor status is covered in depth on the dedicated FUT2 page.

Context

The genetic layer is well documented but does not replace a laboratory measurement. Genome shows the markers as technical evidence; they are especially useful for placing a borderline B12 value in context.

What Genome measures. The genotypes at rs602662 (FUT2), rs1801222 (CUBN) and rs11254363 (TCN2).

Related topics

FUT2 (secretor status)Vitamin B9 (folate)rsIDs, microarray and SNP lookup

Sources

  1. 1Hazra et al., 2008 Common variants of FUT2 are associated with plasma vitamin B12 levels. Nature Genetics 40:1160–1162. doi.org/10.1038/ng.210
  2. 2Hazra et al., 2009 Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway. Human Molecular Genetics 18:4677–4687. doi.org/10.1093/hmg/ddp428