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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

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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.

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