Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women

Am J Clin Nutr. 2009 Feb;89(2):634-40. doi: 10.3945/ajcn.2008.26445. Epub 2008 Dec 30.


Background: Vitamin D status, determined on the basis of 25-hydroxyvitamin D [25(OH)D] concentrations, is associated with the risk of several diseases. Vitamin D binding protein (DBP) is the major carrier of vitamin D and its metabolites, but the role of DBP single nucleotide polymorphisms (SNPs) on 25(OH)D concentrations is unclear.

Objective: The objective was to evaluate the association of 2 DBP gene SNPs with 25(OH)D concentrations and explore whether such association varies according to the amount of vitamin D that needs to be transported.

Design: This cross-sectional study included 741 premenopausal white women, mostly of French descent. Plasma 25(OH)D concentrations were measured by radioimmunoassay. DBP-1 (rs7041) and DBP-2 (rs4588) were genotyped with a Sequenom MassArray platform. Associations and interactions were modeled by using multivariate linear regression.

Results: DBP-1 and DBP-2 SNPs were in strong linkage disequilibrium and were both associated with 25(OH)D concentrations. An additional copy of the rare allele of DBP-1 or DBP-2 was associated with lower 25(OH)D concentrations (beta = -3.29, P for trend = 0.0003; beta = -4.22, P for trend < 0.0001, respectively). These DBP polymorphisms explained as much of the variation in circulating 25(OH)D as did total vitamin D intake (r2 = 1.3% for DBP-1, r2 = 2.0% for DBP-2, and r2 < or = 1.2% for vitamin D intake).

Conclusion: Circulating 25(OH)D concentrations in premenopausal women are strongly related to DBP polymorphisms. Whether DBP rare allele carriers have a different risk of vitamin D-related diseases and whether such carriers can benefit more or less from dietary interventions, vitamin D supplementation, or sun exposure need to be clarified.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Cross-Sectional Studies
  • Female
  • Humans
  • Linear Models
  • Linkage Disequilibrium
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide*
  • Premenopause / blood
  • Vitamin D / administration & dosage*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D-Binding Protein / genetics*
  • Vitamin D-Binding Protein / metabolism


  • Vitamin D-Binding Protein
  • Vitamin D
  • 25-hydroxyvitamin D