Race, genetics explained variations in 25-hydroxyvitamin D

Community-dwelling black Americans demonstrated lower levels of total 25-hydroxyvitamin D and vitamin D-binding protein compared with whites, according to researchers.

These racial differences provide an explanation for a common genetic polymorphism, according to cross-sectional data from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study.

“Race explained 22.7% of the variation in total 25-hydroxyvitamin D levels in an unadjusted model,” Camille E. Powe, MD, of the department of medicine at Brigham and Women’s Hospital, and colleagues wrote.

“Because levels of total 25-hydroxyvitamin D are consistently lower in black Americans than in white Americans, blacks are frequently classified as vitamin D-deficient. … We found that levels of vitamin D-binding protein are also lower in blacks, probably because of the high prevalence of a common genetic variant,” they wrote. “Therefore, low levels of total 25-hydroxyvitamin D probably do not indicate true vitamin D deficiency. … Bioavailable 25-hydroxyvitamin D may be a more appropriate cross-racial marker of vitamin D sufficiency.”

Levels of total 25-(OH)D, vitamin D-binding protein, parathyroid hormone and bone mineral density were measured in blacks (n=1,181) and whites (n=904). In addition, each patient was screened for two common single nucleotide polymorphisms in the vitamin D-binding protein gene (rs7041 and rs4588), according to data.

Mean levels of total 25-(OH)D and vitamin D-binding protein were lower in blacks compared with whites (total 25-[OH]D, 15.6 ng/mL vs. 25.8 ng/mL, P<.001; vitamin D-binding protein, 168 mcg/mL vs. 337 mcg/mL, P<.001), according to data.

Genetic polymorphisms also appeared to explain 79.4% of the variations in vitamin D-binding protein; 9.9% in total 25-(OH)D, according to data.

Black patients tended to have greater BMD (1.05 g/cm2 vs. 0.94 g/cm2, P<.001) compared with whites, researchers added.

BMD was not associated with levels of bioavailable or 25-(OH)D in black homozygous patients, researchers wrote. However, BMD appeared to increase with increasing levels of total or bioavailable 25-(OH)D in whites. Moreover, homozygous patients displayed similar levels of bioavailable 25-(OH)D overall (2.9 ng/mL in blacks vs. 3.1 ng/mL in whites; P=.71) and within quintiles of parathyroid hormone concentration.

In an accompanying editorial, Michael F. Holick, MD, PhD, of the department of medicine, section of endocrinology, nutrition and diabetes, and the Vitamin D, Skin and Bone Research Laboratory at Boston University Medical Center, wrote that vitamin D deficiency has become a global health issue that is associated with metabolic bone disease and other chronic illnesses.

“A perplexing paradox is that blacks have a higher bone mineral density but lower 25-hydroxyvitamin D levels than whites,” Holick wrote.

He concluded that more research is needed to fully appreciate what bioavailable vs. total vitamin D status means for 25-(OH)D and 1,25-(OH)D.

For more information:

Holick MF. N Engl J Med. 2013;369;21:2047-2048.

Powe CE. N Engl J Med. 2013;369;21:1991-2000.

Disclosure: Four of the researchers report being co-inventors on a patent pending on the use of bioavailable vitamin D for the assessment of vitamin D status. Holick reports no relevant financial disclosures.

Clifford J. Rosen, MD

Clifford J. Rosen

  • There has long been controversy concerning the relative value of measuring a serum vitamin D levels to assess insufficiency in specific ethnic and racial groups. For example, black patients have lower levels of total serum 25-(OH)D than whites across all age groups, and if one uses a cutoff of 30 ng/mL for total 25-(OH)D to define vitamin D insufficiency, nearly 96% of black Americans would be considered deficient or insufficient. Many of these same individuals will also have high levels of parathyroid hormone. Yet, black Americans have much greater bone mass than whites, and their risk for osteoporotic fractures is considerably lower than whites.

    In the paper by Powe and colleagues recently published in the New England Journal of Medicine, the authors examined this question by measuring  total serum 25-(OH)D and serum vitamin D-binding protein in a large cohort of black and white Americans. They also assessed polymorphisms in the vitamin D-binding protein and related those differences to serum total and bioactive vitamin D (done by calculating the concentration of total 25-[OH]D and vitamin D-binding protein).

    Powe and colleagues provide clear evidence that racial differences in serum 25-(OH)D are due to common genetic polymorphisms, and that bioavailable 25-(OH)D may be a better indicator for determining insufficiency. Thus, screening individuals for low vitamin D using the conventional serum 25-(OH)D measurement may lead to erroneous results. A new assay to measure free or bioavailable 25-(OH)D will be needed to determine the true prevalence of vitamin D insufficiency in various populations and ethnic groups.

    • Clifford J. Rosen, MD
    • Director of clinical and translational research; senior scientist
      Maine Medical Center’s Research Institute
  • Disclosures: Rosen reports no relevant financial disclosures.