We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Vitamin D binding protein genotype and osteoporosis.
- Authors
Yue Fang; van Meurs, Joyce B. J.; Arp, Pascal; van Leeuwen, Johannes P. T.; Hofman, Albert; Pols, Huibert A. P.; Uitterlinden, André G.; Fang, Yue; Uitterlinden, André G
- 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)D3 for haplotype 1 ( P = 3 × 10−4) and haplotype 2 ( P = 3 × 10−6), respectively. Similar associations were observed for 1,25-(OH)2D3. 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.
- Subjects
NETHERLANDS; OSTEOPOROSIS; BONE diseases; VITAMIN D; CARRIER proteins; HOMEOSTASIS; BONE metabolism; BONES; DIETARY calcium; CELL receptors; COMPARATIVE studies; DISEASE susceptibility; SPONTANEOUS fractures; GENES; GENETIC polymorphisms; GENETICS; LONGITUDINAL method; RESEARCH methodology; MEDICAL cooperation; RADIOGRAPHY; RESEARCH; EVALUATION research; BONE density
- Publication
Calcified Tissue International, 2009, Vol 85, Issue 2, p85
- ISSN
0171-967X
- Publication type
journal article
- DOI
10.1007/s00223-009-9251-9