Is the CYP2R1 rs10741657 G allele associated with lower 25-hydroxyvitamin D?

CYP2R1 rs10741657 is a common genetic marker relevant to vitamin D biology. For a 69-year-old woman, its main implication is a modest population-level predisposition toward lower measured 25-hydroxyvitamin D [25(OH)D], not a diagnosis of deficiency or a substitute for laboratory assessment.

Clinical association

• The G allele is supported as being associated with lower circulating 25(OH)D. A meta-analysis of 16 studies including 52,417 participants found lower 25(OH)D among G-allele carriers, including GG versus AA, and modestly higher odds of vitamin D deficiency (OR 1.09, 95% CI 1.03–1.15).
• Cohort findings generally align with this direction; in a pregnancy supplementation study, each additional G allele was associated with 5.2 nmol/L lower achieved 25(OH)D after cholecalciferol. However, genotype effects and supplementation responses varied across populations and settings.

Mechanistic interpretation

• CYP2R1 encodes a major hepatic enzyme that converts vitamin D₂ and D₃ into 25(OH)D, the principal circulating marker of vitamin D status. Reduced efficiency of this step would be expected to lower serum 25(OH)D.
• Rare CYP2R1 coding variants with reduced enzyme activity impair 25(OH)D production after vitamin D dosing, and hepatic CYP2R1 expression correlates with serum 25(OH)D₃ in liver-biopsy research.
• For rs10741657 specifically, reduced hepatic 25-hydroxylation remains plausible rather than directly proven: it is noncoding, and there are no allele-specific liver expression, protein, or enzymatic-function data establishing that the G allele reduces CYP2R1 activity.

Bottom line

• rs10741657 G is a credible marker of slightly lower 25(OH)D, with a biologically coherent but unproven hepatic mechanism. Clinical decisions should be guided by measured 25(OH)D and individual clinical factors rather than genotype alone.