Vitamin D-binding protein deficiency and homozygous deletion of the GC gene

Alan N. Baer; Suzanne Jan De Beur

doi:10.1056/NEJMc1905282

Vitamin D-binding protein deficiency and homozygous deletion of the GC gene

School of Medicine

Research output: Contribution to journal › Letter › peer-review

Original language	English (US)
Pages (from-to)	2582-2583
Number of pages	2
Journal	New England Journal of Medicine
Volume	380
Issue number	26
DOIs	https://doi.org/10.1056/NEJMc1905282
State	Published - Jun 27 2019

ASJC Scopus subject areas

Medicine(all)

Access to Document

10.1056/NEJMc1905282

Cite this

@article{e98941e139dc4b2d9993cfe6dd56002c,

title = "Vitamin D-binding protein deficiency and homozygous deletion of the GC gene",

author = "Baer, {Alan N.} and {Jan De Beur}, Suzanne",

note = "Funding Information: 25(OH)D remained comparatively stable. Repeated-measures analysis confirmed that changes in vitamin D–binding protein correlated with changes in 25(OH)D between patients (repeated-measures correlation, 0.81; P=0.002), and vitamin D– binding protein and 25(OH)D levels at all time points were strongly correlated (Fig. 1B), with no correlation between 25(OH)D and PTH (repeated-measures correlation, −0.10; P=0.35). Moreover, mean (±SD) levels of PTH, calcium, and free 25(OH)D were normal (58±44 pg per milliliter, 8.5±0.9 mg per deciliter [2.12±0.22 mmol per liter], and 9.2±6.9 pg per milliliter, respectively), similar to those reported in patients with liver cirrhosis.2 (Our study was supported by a grant [R01 DK094486] from the National Institutes of Health.) Animal models3 and persons2 with genetic or acquired deficiency of vitamin D–binding protein provide excellent examples of the free-hormone hypothesis at work. Namely, they suggest that the unbound subset of 25(OH)D is the form that maintains homeostasis of bone and mineral metabolism. Our collective findings imply that in healthy states in which vitamin D–binding protein levels are unchanged, total 25(OH)D correlates with free 25(OH)D4; however, in critical illness or other chronic inflammatory states in which vitamin D–binding protein is decreased, 25(OH)D levels are largely determined by vitamin D–binding protein levels and only modestly correlate with free 25(OH)D. Analogous to evaluation of thyroid function (measuring free T4 instead of total T4), clinical sufficiency of 25(OH)D in sick patients is best determined by methods that measure the unbound fraction.",

year = "2019",

month = jun,

day = "27",

doi = "10.1056/NEJMc1905282",

language = "English (US)",

volume = "380",

pages = "2582--2583",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachussetts Medical Society",

number = "26",

}

TY - JOUR

T1 - Vitamin D-binding protein deficiency and homozygous deletion of the GC gene

AU - Baer, Alan N.

AU - Jan De Beur, Suzanne

N1 - Funding Information: 25(OH)D remained comparatively stable. Repeated-measures analysis confirmed that changes in vitamin D–binding protein correlated with changes in 25(OH)D between patients (repeated-measures correlation, 0.81; P=0.002), and vitamin D– binding protein and 25(OH)D levels at all time points were strongly correlated (Fig. 1B), with no correlation between 25(OH)D and PTH (repeated-measures correlation, −0.10; P=0.35). Moreover, mean (±SD) levels of PTH, calcium, and free 25(OH)D were normal (58±44 pg per milliliter, 8.5±0.9 mg per deciliter [2.12±0.22 mmol per liter], and 9.2±6.9 pg per milliliter, respectively), similar to those reported in patients with liver cirrhosis.2 (Our study was supported by a grant [R01 DK094486] from the National Institutes of Health.) Animal models3 and persons2 with genetic or acquired deficiency of vitamin D–binding protein provide excellent examples of the free-hormone hypothesis at work. Namely, they suggest that the unbound subset of 25(OH)D is the form that maintains homeostasis of bone and mineral metabolism. Our collective findings imply that in healthy states in which vitamin D–binding protein levels are unchanged, total 25(OH)D correlates with free 25(OH)D4; however, in critical illness or other chronic inflammatory states in which vitamin D–binding protein is decreased, 25(OH)D levels are largely determined by vitamin D–binding protein levels and only modestly correlate with free 25(OH)D. Analogous to evaluation of thyroid function (measuring free T4 instead of total T4), clinical sufficiency of 25(OH)D in sick patients is best determined by methods that measure the unbound fraction.

PY - 2019/6/27

Y1 - 2019/6/27

UR - http://www.scopus.com/inward/record.url?scp=85068241793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068241793&partnerID=8YFLogxK

U2 - 10.1056/NEJMc1905282

DO - 10.1056/NEJMc1905282

M3 - Letter

C2 - 31242372

AN - SCOPUS:85068241793

VL - 380

SP - 2582

EP - 2583

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 26

ER -

Vitamin D-binding protein deficiency and homozygous deletion of the GC gene

ASJC Scopus subject areas

Access to Document

Other files and links

Cite this