Vitamin D (synthesis, transport, receptor)

GC · DHCR7 · CYP2R1 · VDR

Genes involved in synthesis, transport and breakdown contribute to variation in vitamin D levels. One study found low 25(OH)D more often in the group with the highest combined genetic score than in the group with the lowest score. This group comparison does not predict an individual's blood level. GC and VDR are covered in more detail on separate pages.

Key points

GC (rs2282679) is by far the strongest genetic influence on the 25(OH)D level.
In one study, the highest combined genotype score was associated with more frequent low 25(OH)D levels.
None of these markers replaces measuring 25(OH)D in blood.

#The chain of four stations

A genome-wide study of around 34,000 people confirmed associations between 25(OH)D levels and variants in GC, DHCR7 and CYP2R1. Values below 75 nmol/L were more common in the top quartile of a combined genotype score than in the bottom quartile (OR 2.47; Wang 2010). This is a group comparison from that study, not an individual risk prediction. The markers rs2282679 (GC), rs12785878 (near DHCR7) and rs10741657 (near CYP2R1) relate to different parts of vitamin D metabolism. Evidence for rs6013897 near CYP24A1 and several VDR markers is less consistent.

#What it means

Genotype and blood measurement answer different questions. These markers are associated with average differences in studied groups; a 25(OH)D test measures the current blood level. The variants listed here alone do not establish deficiency or indicate supplementation.

#Context

The level loci (GC, DHCR7, CYP2R1) are very well documented; the VDR receptor associations remain weaker and inconsistent. For depth see the dedicated pages on GC (binding protein) and VDR (receptor). Genome shows all markers as technical evidence.

What Genome measures. The genotypes at rs2282679 (GC), rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1) and at the VDR markers FokI, BsmI, ApaI and TaqI.

Sources

1Wang et al., 2010 Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet 376:180-188. doi.org/10.1016/S0140-6736(10)60588-0