Vitamin D binding protein genotype and osteoporosis.
Vitamin D binding protein genotype and osteoporosis.
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DOI：
10.1007/s00223-009-9251-9
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发表时间：
2009-08
影响因子：
4.2
通讯作者：
Uitterlinden, Andre G.
中科院分区：
文献类型：
--
作者：
Fang, Yue;van Meurs, Joyce B. J.;Arp, Pascal;van Leeuwen, Johannes P. T.;Hofman, Albert;Pols, Huibert A. P.;Uitterlinden, Andre G.
骨质疏松症是一种导致骨折风险增加的骨骼疾病。它被认为是一种复杂的多因素遗传性疾病，具有环境和遗传因素的相互作用。作为骨质疏松症的候选基因，我们研究了维生素D结合蛋白（DBP，或组特异性组分，Gc），它结合并将维生素D转运到靶组织，通过维生素D内分泌系统维持钙稳态。DBP也可以转化为DBP-巨噬细胞活化因子（DBP-MAF），其通过直接活化破骨细胞介导骨吸收。总结了DBP基因的遗传连锁结构。我们对6,181名老年白种人的两个单核苷酸多态性（SNPs，rs7041 = Glu 416 Asp和rs 4588 = Thr 420 Lys）进行了基因分型，并研究了DBP基因型与维生素D受体（VDR）基因型和膳食钙摄入量与骨折风险的相互作用。DBP SNP的单倍型对应于称为Gc 1 s（单倍型1）、Gc 2（单倍型2）和Gc 1f（单倍型3）的蛋白质变异。在1,312名受试者的亚组中，发现DBP基因型分别与单倍型1（P = 3 × 10−4）和单倍型2（P = 3 × 10−6）的血清25-（OH）D3升高和降低相关。在1，25-（OH）2D 3中观察到类似的关联。在整个研究人群中，DBP基因型与骨折风险无显著相关性。然而，我们观察到DBP和VDR单倍型在确定骨折风险方面的相互作用。在DBP单倍型1-携带者组中，纯合子VDR阻滞5-单倍型1的受试者与非携带者相比骨折风险增加33%（P = 0.005）。在膳食钙摄入量<1.09 g/d的亚组中，DBP hap 1纯合子与非携带者骨折风险的风险比（95%置信区间）为1.47（1.06-2.05）。所有协会都是独立的年龄和性别。我们的研究表明，DBP基因对骨折风险的遗传效应仅在与骨代谢的其他遗传和环境风险因素相结合时才出现。
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.
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影响因子：
6.2
作者：
Fang, Y;Van Meurs, JBJ;Uitterlinden, AG
通讯作者：
Uitterlinden, AG
影响因子：
15.9
作者：
BOUILLON, R;VANASSCHE, FA;DEMOOR, P
通讯作者：
DEMOOR, P
影响因子：
6.2
作者：
Lauridsen, AL;Vestergaard, P;Nexo, E
通讯作者：
Nexo, E
影响因子：
120.7
作者：
Ioannidis, JPA;Ralston, SH;Uitterlinden, AG
通讯作者：
Uitterlinden, AG
影响因子：
4
作者：
MCCLOSKEY, EV;SPECTOR, TD;KANIS, JA
通讯作者：
KANIS, JA