Vitamin D-binding protein and vitamin D status of black Americans and white Americans

Abstract

Background: Low levels of total 25-hydroxyvitamin D are common among black Americans. Vitamin D-binding protein has not been considered in the assessment of vitamin D deficiency.

Methods: In the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort of blacks and whites (2085 participants), we measured levels of total 25-hydroxyvitamin D, vitamin D-binding protein, and parathyroid hormone as well as bone mineral density (BMD). We genotyped study participants for two common polymorphisms in the vitamin D-binding protein gene (rs7041 and rs4588). We estimated levels of bioavailable 25-hydroxyvitamin D in homozygous participants.

Results: Mean (±SE) levels of both total 25-hydroxyvitamin D and vitamin D-binding protein were lower in blacks than in whites (total 25-hydroxyvitamin D, 15.6±0.2 ng per milliliter vs. 25.8±0.4 ng per milliliter, P<0.001; vitamin D-binding protein, 168±3 μg per milliliter vs. 337±5 μg per milliliter, P<0.001). Genetic polymorphisms independently appeared to explain 79.4% and 9.9% of the variation in levels of vitamin D-binding protein and total 25-hydroxyvitamin D, respectively. BMD was higher in blacks than in whites (1.05±0.01 g per square centimeter vs. 0.94±0.01 g per square centimeter, P<0.001). Levels of parathyroid hormone increased with decreasing levels of total or bioavailable 25-hydroxyvitamin D (P<0.001 for both relationships), yet within each quintile of parathyroid hormone concentration, blacks had significantly lower levels of total 25-hydroxyvitamin D than whites. Among homozygous participants, blacks and whites had similar levels of bioavailable 25-hydroxyvitamin D overall (2.9±0.1 ng per milliliter and 3.1±0.1 ng per milliliter, respectively; P=0.71) and within quintiles of parathyroid hormone concentration.

Conclusions: Community-dwelling black Americans, as compared with whites, had low levels of total 25-hydroxyvitamin D and vitamin D-binding protein, resulting in similar concentrations of estimated bioavailable 25-hydroxyvitamin D. Racial differences in the prevalence of common genetic polymorphisms provide a likely explanation for this observation. (Funded by the National Institute on Aging and others.).

Figure 1. Levels of Total 25-Hydroxyvitamin D and Vitamin D-Binding Protein in Community-Dwelling White and Black Study Participants

Histograms representing stacked distributions are shown. Mean (±SE) levels of total 25-hydroxyvitamin D were significantly lower in blacks than in whites (15.6±0.2 ng per milliliter vs. 25.8±0.4 ng per milliliter, P<0.001) (Panel A), as were levels of vitamin D-binding protein (168±3 μg per milliliter vs. 337±5 μg per milliliter, P<0.001) (Panel B).

Figure 2. Variant Vitamin D–Binding Proteins and Bioavailable 25-Hydroxyvitamin D

As shown in Panel A, unique combinations of the rs7041 and rs4588 polymorphisms produce amino acid changes resulting in variant vitamin D–binding proteins (left side of panel; Asp denotes aspartic acid, Glu glutamic acid, Lys lysine, and Thr threonine). The Gc1F phenotype was most common in black homozygotes, whereas the Gc1S phenotype was most common in white homozygotes (right side of panel). As shown in Panel B, levels of vitamin D–binding protein were lowest in Gc1F/Gc1F homozygotes (632 participants, 93±2 μg per milliliter), highest in Gc1S/Gc1S homozygotes (313 participants, 468±6 μg per milliliter), and intermediate in Gc2/Gc2 homozygotes (80 participants, 190±4 μg per milliliter). Plasma vitamin D–binding protein concentrations in Gc1F/Gc1S heterozygotes (413 participants, 285±4 μg per milliliter) were intermediate between those of Gc1F/Gc1F homozygotes and Gc1S/Gc1S homozygotes. These differences were significant (P<0.001 for all comparisons). Panel C shows a histogram representing stacked distributions. Among homozygous participants, levels of bioavailable 25-hydroxyvitamin D were similar in blacks and whites (2.9±0.1 ng per milliliter in blacks and 3.1±0.1 ng per milliliter in whites, P = 0.71).

Figure 3. Total and Bioavailable 25-Hydroxyvitamin D Levels among Homozygous Blacks and Whites with Similar Parathyroid Hormone Levels

Within quintiles of parathyroid hormone values, blacks generally had lower levels of total 25-hydroxyvitamin D levels than whites (Panel A) but similar levels of bioavailable 25-hydroxyvitamin D (Panel B). I bars indicate standard errors. One asterisk denotes P<0.01 for the comparisons between blacks and whites within the quintile, two asterisks P<0.01 for the comparison with the highest quintile among whites, and three asterisks P<0.01 for the comparison with the highest quintile among blacks.