Vitamin D binding protein genotype is associated with serum 25-hydroxyvitamin D and PTH concentrations, as well as bone health in children and adolescents in Finland

PLoS One. 2014 Jan 30;9(1):e87292. doi: 10.1371/journal.pone.0087292. eCollection 2014.

Abstract

Vitamin D binding protein (DBP)/group-specific component (Gc), correlates positively with serum vitamin D metabolites, and phenotype influences serum 25-hydroxyvitamin D (S-25(OH)D) concentration. The protein isoform has been associated with decreased bone mineral density (BMD) and increased fracture risk. We examined the role of GC genotypes in S-25(OH)D status and BMD in 231 Finnish children and adolescents aged 7-19 yr. BMD was measured with DXA from lumbar spine (LS), total hip, and whole body, and for 175 subjects, radial volumetric BMD was measured with pQCT. Background characteristic and total dietary intakes of vitamin D and calcium were collected. The concentrations of 25(OH)D, parathyroid hormone (PTH), calcium and other markers of calcium homeostasis were determined from blood and urine. Genotyping was based on single-nucleotide polymorphism (rs4588) in the GC gene. The genotype distribution was: GC 1/1 68%, GC 1/2 26% and GC 2/2 6%. A significant difference emerged in 25(OH)D and PTH concentrations between the genotypes, (p = 0.001 and 0.028 respectively, ANCOVA). There was also a linear trend in: Gc 2/2 had the lowest 25(OH)D and PTH concentrations (p = 0.025 and 0.012, respectively). Total hip bone mineral content was associated with GC genotype (BMC) (p = 0.05, ANCOVA) in boys. In regression analysis, after adjusting for relevant covariates, GC genotype was associated with LS BMC and strength and strain index (SSI) Z-score in both genders, and LS BMD in boys. In conclusion, the present study demonstrates the association between GC genotypes and S-25(OH)D and PTH concentrations. The results show the influence of DBP genetic variation on bone mass accrual in adolescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Alleles
  • Bone Density / genetics*
  • Bone and Bones
  • Calcium, Dietary / metabolism
  • Child
  • Female
  • Finland
  • Genotype
  • Humans
  • Male
  • Parathyroid Hormone / blood*
  • Parathyroid Hormone / genetics
  • Parathyroid Hormone / metabolism
  • Polymorphism, Single Nucleotide / genetics
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D / genetics
  • Vitamin D / metabolism
  • Vitamin D-Binding Protein / genetics*
  • Vitamin D-Binding Protein / metabolism

Substances

  • Calcium, Dietary
  • Parathyroid Hormone
  • Vitamin D-Binding Protein
  • Vitamin D
  • 25-hydroxyvitamin D

Grants and funding

This work was financially supported by the Foundation for Pediatric Research, the Yrjö Jahnsson Foundation, the Academy of Finland, the Helsinki University Hospital research funds, the Sigrid Juselius Foundation, the Ella and Georg Ehrnrooth Foundation, the University of Helsinki Research Foundation, the Maud Kuistila Memorial Foundation, the Folkhälsan Research Foundation, National Doctoral Programme of Musculoskeletal Disorders and Biomaterials (TBDP) and the Finnish Graduate School on Applied Biosciences (ABS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.