Pekkinen Minna, Saarnio Elisa, Viljakainen Heli T, Kokkonen Elina, Jakobsen Jette, Cashman Kevin, Mäkitie Outi, Lamberg-Allardt Christel
Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland ; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.
Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.
PLoS One. 2014 Jan 30;9(1):e87292. doi: 10.1371/journal.pone.0087292. eCollection 2014.
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.
维生素D结合蛋白（DBP）/群体特异性成分（Gc）与血清维生素D代谢产物呈正相关，且其表型会影响血清25-羟基维生素D（S-25(OH)D）浓度。该蛋白质异构体与骨矿物质密度（BMD）降低及骨折风险增加有关。我们研究了GC基因型在231名7至19岁芬兰儿童和青少年的S-25(OH)D状态及BMD中的作用。采用双能X线吸收法（DXA）测量腰椎（LS）、全髋和全身的骨密度，对175名受试者采用外周定量计算机断层扫描（pQCT）测量桡骨体积骨密度。收集背景特征以及维生素D和钙的总膳食摄入量。测定血液和尿液中25(OH)D、甲状旁腺激素（PTH）、钙及其他钙稳态标志物的浓度。基因分型基于GC基因中的单核苷酸多态性（rs4588）。基因型分布为：GC 1/1占68%，GC 1/2占26%，GC 2/2占6%。各基因型之间的25(OH)D和PTH浓度出现显著差异（分别为p = 0.001和0.028，协方差分析）。此外还存在线性趋势：Gc 2/2的25(OH)D和PTH浓度最低（分别为p = 0.025和0.012）。在男孩中，全髋骨矿物质含量与GC基因型（BMC）相关（p = 0.05，协方差分析）。在回归分析中，调整相关协变量后，GC基因型在男女中均与LS BMC、强度和应变指数（SSI）Z评分相关，在男孩中还与LS BMD相关。总之，本研究证明了GC基因型与S-25(OH)D和PTH浓度之间的关联。结果显示了DBP基因变异对青春期骨量积累的影响。
