Genetics contribute to racial disparities in vitamin D status of children

Race is known to be a significant risk factor in vitamin D deficiency. African American and Hispanic children are more likely to have insufficient levels of vitamin D than white children.

To find out what role genetics play in these racial differences, a team of MUSC investigators focused on a key protein involved in vitamin D metabolism known as the vitamin D-binding protein.

In an article in Pediatric Research, the team reports that many African American children have a variation of the protein that is linked to low vitamin D levels. Even when children with this variation met the daily recommended allowance of vitamin D, they were still vitamin D insufficient.

These results suggest that children with this variation may need to be supplemented with higher doses of vitamin D to reach vitamin D “sufficiency” as defined by the Endocrine Society.

Vitamin D promotes healthy bone development in children and is mostly obtained through sun exposure or dietary supplements. Not getting enough vitamin D can lead to bone disease and many other health problems in children and adults.

Vitamin D-binding protein transports 85 to 90 percent of vitamin D metabolites in the blood, and many different versions, or alleles, of its gene sequence have been identified.

“It’s known that vitamin D-binding protein has many different alleles in the human population, and we wanted to see if those alleles contributed to vitamin D status in children who were meeting the recommended daily allowance of intake,” explained Dan Newton, Ph.D., a scientist in the Department of Pediatrics at MUSC and the first author of the study.

The three most commonly studied vitamin D-binding protein alleles are 1F, 1S and 2. The 1F allele is found primarily in humans of African ancestry, while the 1S and 2 alleles are usually associated with European or Asian ancestry. Humans get one allele from each parent for every gene in their DNA.

“Other people have shown differences in the response to vitamin D based on these alleles, but it had never been shown in children,” said Carol Wagner, M.D., a neonatologist at MUSC Children’s Health and a senior author of the study.

The study, funded by the Thrasher Research Fund, enrolled 123 male and female children between the ages of 1 and 8 years old. Their dietary intake of vitamin D and daily sun exposure were recorded at each visit.

Study visits took place in the Nexus Research Center at MUSC, which provides laboratory space and clinical resources for many studies on campus, with the support of the South Carolina Clinical & Translational Research Institute.

Children with two copies of the 1S allele – who were mostly white – had the highest vitamin D status and were most likely to reach vitamin D sufficiency, even with low daily intake.

“In our study, about 75 percent of the African American children had both alleles that were 1F. We noticed that when they were taking the recommended daily allowance of vitamin D, which is defined as 600 IU, very few reached sufficiency." 

Dan Newton, Ph.D.

In contrast, children with the 1F allele – who were mostly African American – had a lower vitamin D status, regardless of their dietary intake of vitamin D. Furthermore, children with two copies of the 1F allele had the lowest overall vitamin D status.

“In our study, about 75 percent of the African American children had both alleles that were 1F,” said Newton. “We noticed that when they were taking the recommended daily allowance of vitamin D, which is defined as 600 IU, very few reached sufficiency.”

Remarkably, just having one copy of the 1S allele was associated with a significantly higher vitamin D status than if the child did not have a copy of it.

“The main surprise to me was that if the African American children had the 1S allele, then the recommended daily allowance made them vitamin D sufficient,” Newton said.

When asked about the main takeaway from the study, Newton said, “Your ancestry may have a direct impact on your vitamin D status.”

“With that knowledge I think people can better make informed decisions about taking higher doses of vitamin D.”

"We’re not recommending pharmacologic doses. We’re recommending what you would get if you lived in a sun-rich environment and didn’t use sunscreen."

Carol Wagner, M.D.

More research is necessary before public policy changes are made to the daily recommended allowance of vitamin D for children. However, Wagner and her MUSC colleagues have shown in previous work that vitamin D doses as high as 4400 IU/day in pregnant women and 6400 IU/day in lactating and postpartum women have no adverse effects.

“We’re not recommending pharmacologic doses,” Wagner clarified. “We’re recommending what you would get if you lived in a sun-rich environment and didn’t use sunscreen.”

Going forward, Newton plans to investigate other clinical outcomes related to differences in vitamin D-binding protein alleles.

“We have now added vitamin-D binding protein genotyping as a standard parameter in our ongoing and future studies on vitamin D supplementation in pregnant or breastfeeding women and their children,” Newton said.

“Vitamin D-binding protein allelic variability may be an important consideration in data interpretation, especially regarding supplementation responses in infants. These responses may not only involve differences in vitamin D status, but also childhood immunity and other clinical measurements we routinely collect during these clinical trials.”