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Vitamin D binding protein genotype and osteoporosis.
Calcif Tissue Int. 2009 Aug; 85(2):85-93.CT

Abstract

Osteoporosis is a bone disease leading to an increased fracture risk. It is considered a complex multifactorial genetic disorder with interaction of environmental and genetic factors. As a candidate gene for osteoporosis, we studied vitamin D binding protein (DBP, or group-specific component, Gc), which binds to and transports vitamin D to target tissues to maintain calcium homeostasis through the vitamin D endocrine system. DBP can also be converted to DBP-macrophage activating factor (DBP-MAF), which mediates bone resorption by directly activating osteoclasts. We summarized the genetic linkage structure of the DBP gene. We genotyped two single-nucleotide polymorphisms (SNPs, rs7041 = Glu416Asp and rs4588 = Thr420Lys) in 6,181 elderly Caucasians and investigated interactions of the DBP genotype with vitamin D receptor (VDR) genotype and dietary calcium intake in relation to fracture risk. Haplotypes of the DBP SNPs correspond to protein variations referred to as Gc1s (haplotype 1), Gc2 (haplotype 2), and Gc1f (haplotype3). In a subgroup of 1,312 subjects, DBP genotype was found to be associated with increased and decreased serum 25-(OH)D(3) for haplotype 1 (P = 3 x 10(-4)) and haplotype 2 (P = 3 x 10(-6)), respectively. Similar associations were observed for 1,25-(OH)(2)D(3). The DBP genotype was not significantly associated with fracture risk in the entire study population. Yet, we observed interaction between DBP and VDR haplotypes in determining fracture risk. In the DBP haplotype 1-carrier group, subjects of homozygous VDR block 5-haplotype 1 had 33% increased fracture risk compared to noncarriers (P = 0.005). In a subgroup with dietary calcium intake <1.09 g/day, the hazard ratio (95% confidence interval) for fracture risk of DBP hap1-homozygote versus noncarrier was 1.47 (1.06-2.05). All associations were independent of age and gender. Our study demonstrated that the genetic effect of the DBP gene on fracture risk appears only in combination with other genetic and environmental risk factors for bone metabolism.

Authors+Show Affiliations

Department of Internal Medicine, Erasmus Medical Center, Genetic Laboratory, Rotterdam, The Netherlands. fangnl@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19488670

Citation

Fang, Yue, et al. "Vitamin D Binding Protein Genotype and Osteoporosis." Calcified Tissue International, vol. 85, no. 2, 2009, pp. 85-93.
Fang Y, van Meurs JB, Arp P, et al. Vitamin D binding protein genotype and osteoporosis. Calcif Tissue Int. 2009;85(2):85-93.
Fang, Y., van Meurs, J. B., Arp, P., van Leeuwen, J. P., Hofman, A., Pols, H. A., & Uitterlinden, A. G. (2009). Vitamin D binding protein genotype and osteoporosis. Calcified Tissue International, 85(2), 85-93. https://doi.org/10.1007/s00223-009-9251-9
Fang Y, et al. Vitamin D Binding Protein Genotype and Osteoporosis. Calcif Tissue Int. 2009;85(2):85-93. PubMed PMID: 19488670.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D binding protein genotype and osteoporosis. AU - Fang,Yue, AU - van Meurs,Joyce B J, AU - Arp,Pascal, AU - van Leeuwen,Johannes P T, AU - Hofman,Albert, AU - Pols,Huibert A P, AU - Uitterlinden,André G, Y1 - 2009/06/02/ PY - 2008/08/20/received PY - 2009/04/16/accepted PY - 2009/6/3/entrez PY - 2009/6/3/pubmed PY - 2009/10/21/medline SP - 85 EP - 93 JF - Calcified tissue international JO - Calcif. Tissue Int. VL - 85 IS - 2 N2 - Osteoporosis is a bone disease leading to an increased fracture risk. It is considered a complex multifactorial genetic disorder with interaction of environmental and genetic factors. As a candidate gene for osteoporosis, we studied vitamin D binding protein (DBP, or group-specific component, Gc), which binds to and transports vitamin D to target tissues to maintain calcium homeostasis through the vitamin D endocrine system. DBP can also be converted to DBP-macrophage activating factor (DBP-MAF), which mediates bone resorption by directly activating osteoclasts. We summarized the genetic linkage structure of the DBP gene. We genotyped two single-nucleotide polymorphisms (SNPs, rs7041 = Glu416Asp and rs4588 = Thr420Lys) in 6,181 elderly Caucasians and investigated interactions of the DBP genotype with vitamin D receptor (VDR) genotype and dietary calcium intake in relation to fracture risk. Haplotypes of the DBP SNPs correspond to protein variations referred to as Gc1s (haplotype 1), Gc2 (haplotype 2), and Gc1f (haplotype3). In a subgroup of 1,312 subjects, DBP genotype was found to be associated with increased and decreased serum 25-(OH)D(3) for haplotype 1 (P = 3 x 10(-4)) and haplotype 2 (P = 3 x 10(-6)), respectively. Similar associations were observed for 1,25-(OH)(2)D(3). The DBP genotype was not significantly associated with fracture risk in the entire study population. Yet, we observed interaction between DBP and VDR haplotypes in determining fracture risk. In the DBP haplotype 1-carrier group, subjects of homozygous VDR block 5-haplotype 1 had 33% increased fracture risk compared to noncarriers (P = 0.005). In a subgroup with dietary calcium intake <1.09 g/day, the hazard ratio (95% confidence interval) for fracture risk of DBP hap1-homozygote versus noncarrier was 1.47 (1.06-2.05). All associations were independent of age and gender. Our study demonstrated that the genetic effect of the DBP gene on fracture risk appears only in combination with other genetic and environmental risk factors for bone metabolism. SN - 1432-0827 UR - https://www.unboundmedicine.com/medline/citation/19488670/Vitamin_D_binding_protein_genotype_and_osteoporosis_ L2 - https://dx.doi.org/10.1007/s00223-009-9251-9 DB - PRIME DP - Unbound Medicine ER -