Polymorphisms of the Vitamin D Binding Protein (VDBP) and Free Vitamin D in Patients with Cystic Fibrosis

Nutrients. 2024 Nov 11;16(22):3850. doi: 10.3390/nu16223850.

Abstract

Objectives/background: Vitamin D-binding protein (VDBP) and free vitamin D are new markers that are being studied as a possible markers of vitamin D status. The main aim of our study was to analyze the VDBP genotype and quantify the levels of free vitamin D in a sample of cystic fibrosis (CF) patients.

Methods: We conducted a multicenter, cross-sectional, and prospective study including patients with CF and exocrine pancreatic insufficiency who were clinically stable. We investigated vitamin D levels (total and free) and the different VDBP haplotypes. Free vitamin D levels were measured using an electro-chemiluminescence assay.

Results: A sample of 48 patients was obtained (52% male; median age 13.8 years). The most common allele of VDBP was Gc1s (72%) > Gc2 (52%) > Gc1f (27%). The median calcidiol was 21.2 ng/mL (IR 15.3-26.9), and 81% had levels in the insufficiency range: 23 patients (48%) below 20 ng/mL, and 16 (33%) between 20 and 30 ng/mL. The median free vitamin D level was 4.2 pg/mL (IR 3.9-5.6). A positive correlation was observed between calcidiol and free vitamin D levels (r = 0.871; p < 0.0001). After adjustment for season, vitamin D supplementation, sex, and CF-related diabetes, patients with Gc1f polymorphism had a lower risk of vitamin D deficiency, OR 0.22 (95% CI 0.05-0.99), and p = 0.027. A negative linear trend was observed between the polymorphisms grouped into three categories (Gc1/Gc1, Gc1/Gc2, and Gc2/Gc2, in that order) and vitamin D and free vitamin D levels (p = 0.025 and p = 0.033, respectively).

Conclusion: In CF, as in the general population, the most common VDBP haplotype in the Caucasian race is Gc1s. VDBP polymorphisms influence serum vitamin D and free vitamin D levels in CF patients. There is a good correlation between free vitamin D and calcidiol levels, suggesting that measuring the latter in CF does not seem to provide any additional benefit.

Keywords: VDBP; cystic fibrosis; free vitamin D; free vitamin D hypothesis; vitamin D.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Biomarkers / blood
  • Child
  • Cross-Sectional Studies
  • Cystic Fibrosis* / blood
  • Cystic Fibrosis* / genetics
  • Exocrine Pancreatic Insufficiency / blood
  • Exocrine Pancreatic Insufficiency / genetics
  • Female
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Polymorphism, Genetic
  • Prospective Studies
  • Vitamin D Deficiency* / blood
  • Vitamin D Deficiency* / genetics
  • Vitamin D* / analogs & derivatives
  • Vitamin D* / blood
  • Vitamin D-Binding Protein* / blood
  • Vitamin D-Binding Protein* / genetics
  • Young Adult

Substances

  • Vitamin D-Binding Protein
  • Vitamin D
  • GC protein, human
  • Biomarkers

Grants and funding

This research was funded by the Ernesto Sanchez Villares Foundation; the Society of Pediatrics of Asturias, Cantabria, and Castilla y León (SCCALP), grant number 2020/01 call; and the Spanish Society of Pediatric Gastroenterology Hepatology and Nutrition (SEGHNP) (2021 call).