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

Minna Pekkinen, Elisa Saarnio, Heli T. Viljakainen, Elina Kokkonen, Jette Jakobsen, Kevin Cashman, Outi Makitie, Christel Lamberg-Allardt

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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.
Original languageEnglish
Article numbere87292
JournalPLOS ONE
Volume9
Issue number1
Number of pages10
ISSN1932-6203
DOIs
Publication statusPublished - 2014

Keywords

  • MULTIDISCIPLINARY
  • GROUP-SPECIFIC COMPONENT
  • MINERAL DENSITY
  • GC-GLOBULIN
  • PLASMA-CONCENTRATIONS
  • FRACTURE RISK
  • GENE
  • OSTEOPOROSIS
  • POLYMORPHISM
  • PHENOTYPE
  • GROWTH
  • Finland Europe Palearctic region
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common child, preadolescent child, adolescent female, male
  • human DBP gene [Hominidae] human vitamin D binding protein gene
  • human GC gene [Hominidae] human group-specific component gene single-nucleotide polymorphism
  • 25-hydroxyvitamin D 64719-49-9
  • calcium 7440-70-2
  • parathyroid hormone 9002-64-6
  • vitamin D 1406-16-2
  • 03502, Genetics - General
  • 03508, Genetics - Human
  • 10006, Clinical biochemistry - General methods and applications
  • 10063, Biochemistry studies - Vitamins
  • 10064, Biochemistry studies - Proteins, peptides and amino acids
  • 10067, Biochemistry studies - Sterols and steroids
  • 10069, Biochemistry studies - Minerals
  • 15002, Blood - Blood and lymph studies
  • 15004, Blood - Blood cell studies
  • 17018, Endocrine - Thyroid
  • 18004, Bones, joints, fasciae, connective and adipose tissue - Physiology and biochemistry
  • 18006, Bones, joints, fasciae, connective and adipose tissue - Pathology
  • 25000, Pediatrics
  • Clinical Chemistry
  • Molecular Genetics
  • Orthopedics
  • Pediatrics
  • bone health
  • bone mineral density
  • genetic variation
  • homeostasis
  • stress strain index
  • total dietary intake
  • bone fracture Fractures (MeSH) bone disease, injury etiology
  • Allied Medical Sciences
  • Biochemistry and Molecular Biophysics
  • Human Medicine, Medical Sciences
  • blood blood and lymphatics
  • hip
  • lumbar spine skeletal system
  • serum blood and lymphatics
  • dual X-ray absorptiometry DXA clinical techniques, diagnostic techniques
  • genotyping clinical techniques, diagnostic techniques
  • radial volumetric BMD measurement clinical techniques, diagnostic techniques

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