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,Heli T Viljakainen,Elina Kokkonen,Elisa Saarnio,Outi Mäkitie,Kevin Cashman,Jette Jakobsen,Christel Lamberg-Allardt

doi:10.1371/journal.pone.0087292

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.

Highlights

Low bone mass during adolescence is a risk factor for the development of osteoporosis in later stages of life [1]
The inverse relationship that we discovered between GC genotypes and bone mineral density (BMD) could be caused by the difference in free or bound serum D binding protein (DBP) levels among different genotypes, which can lead to differences in the inhibition of vitamin D action and in osteoclast function by group-specific component (Gc)-MAF activation
The observational design of our study prevented us from establishing a causal relationship between GC genotype, S-25(OH)D, parathyroid hormone (PTH) and bone accrual in adolescence. This is the first study to examine the association between GC genotype on bone health in children and adolescents

Summary

Introduction

Low bone mass during adolescence is a risk factor for the development of osteoporosis in later stages of life [1]. Vitamin D deficiency can have a negative effect on bone remodeling and mineralization [2,3]. Inadequate sun light exposure and nutrition as well as genetic determinants, such as polymorphism of 7dehydrocholesterol reductase, hepatic microsomal enzyme, and vitamin D binding protein (DBP), known as group-specific component (Gc), is associated with vitamin D insufficiency [4]. Serum 25-hydroxyvitamin D [S-25(OH)D] is considered to be the most reliable marker of vitamin D status. S-25(OH)D concentrations are partly genetically determined [5,6,7]. A negative correlation exists between S-25(OH)D and serum parathyroid hormone (S-PTH) concentration [8]. PTH is a strong regulator of bone resorption

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Conclusion