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


METHODS
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).


CONCLUSIONS
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.
Sinotte
Marc
M
Département de Médecine Sociale et Préventive, Université Laval, Québec, Canada.
Diorio
Caroline
C
Bérubé
Sylvie
S
Pollak
Michael
M
Brisson
Jacques
J
D000483:Alleles; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause / Q000097:blood; D014807:Vitamin D / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood; D014809:Vitamin D-Binding Protein / Q000235:genetics* / Q000378:metabolism
D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D