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The Effects of Vitamin D Binding Protein (VDBP) Genotypes on Circulating 25(OH)D and VDBP Levels during Pregnancy
Author(s) -
Wagner Carol L,
Brady Sean K,
Newton Danforth,
Baatz John E,
Shary Judy R,
Hollis Bruce W
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb357
Subject(s) - vitamin d binding protein , vitamin d and neurology , medicine , genotype , pregnancy , vitamin , population , endocrinology , allele , biology , genetics , gene , environmental health
Vitamin D deficiency is widespread and is particularly problematic during pregnancy, because vitamin D plays a major role in the development of the fetus and is associated with greater birth weights and fewer adverse outcomes. There are common polymorphisms in the Vitamin Binding Protein (VDBP) gene, which appear to be linked to 25(OH)D concentrations in the blood (this is the major circulating vitamin D metabolite). We hypothesize that these VDBP genotypes may be important factors to consider in interpretation of data in vitamin D supplementation studies of pregnant women, including any racial/ethnic differences in response. The objective of this study was to determine if specific VDBP polymorphisms are linked with circulating 25(OH)D concentrations during pregnancy. Subjects were pregnant women enrolled in a randomized trial of vitamin D supplementation (400 or 4400 IU/day) at our institution (C.L. Wagner, PI; W.K. Kellogg Foundation, sponsor). Genotypes were determined by RFLP analyses for 3 VDBP polymorphisms (Gc1S, Gc1F, Gc2) using DNA extracted from blood of 122 trial subjects. Plasma VDBP concentrations were determined by ELISA. The genotypes were compared by their associations with mean plasma 25(OH)D and VDBP concentrations using Students' t‐test (significant two‐tailed p‐value <0.05). It was found that there was a wide variation of VDBP alleles found in this population, with distinct racial/ethnic associations. Pregnant women homozygous for the VDBP Gc1S allele had significantly higher circulating 25(OH)D levels, while the Gc1F‐1F genotype, particularly common in African‐Americans, was associated with the lowest concentrations. However, plasma VDBP concentrations were not statistically correlated with genotype. In summary, this study demonstrated that VDBP polymorphisms affect circulating 25(OH)D concentrations in pregnant women (i.e., their “vitamin D status”). Certain genotypes were more common in different races, likely contributing to the known racial/ethnic disparities of vitamin D deficiency. These results strongly suggest that the VDBP genotype, which is relatively easy to analyze, is a valuable factor in interpreting data in vitamin D supplementation studies. Support or Funding Information Funded by the W. K. Kellogg Foundation and by the South Carolina Clinical & Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, NIH/NCAT Grant number UL1 TR000062. Vitamin D study drug and placebo provided by Church & Dwight.