Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women
Genetic polymorphisms of the vitamin D binding protein and plasma concentrations of 25-hydroxyvitamin D in premenopausal women
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DOI：
10.3945/ajcn.2008.26445
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发表时间：
2009-02-01
影响因子：
7.1
通讯作者：
Brisson, Jacques
中科院分区：
文献类型：
--
作者：
Sinotte, Marc;Diorio, Caroline;Brisson, Jacques
背景资料：维生素D状态，根据25-羟基维生素D [25（OH）D]浓度确定，与几种疾病的风险有关。维生素D结合蛋白（DBP）是维生素D及其代谢产物的主要载体，但DBP单核苷酸多态性（SNPs）对25（OH）D浓度的作用尚不清楚。目的：评估DBP基因2个SNPs与25（OH）D浓度的相关性，并探讨这种相关性是否根据需要转运的维生素D量而变化。设计：这项横断面研究包括741名绝经前白色妇女，大多数是法国血统。用放射免疫法测定血浆25（OH）D浓度。使用Sequenom MassArray平台对DBP-1（rs7041）和DBP-2（rs 4588）进行基因分型。结果：DBP-1和DBP-2 SNPs均与25（OH）D浓度呈强连锁不平衡，且均与25（OH）D浓度相关。DBP-1或DBP-2的稀有等位基因的额外拷贝与25（OH）D浓度较低相关（分别为β =-3.29，P = 0.0003; β =-4.22，P = 0.0001）。这些DBP多态性解释了循环中25（OH）D的变化，就像总维生素D摄入量一样（DBP-1的r（2）= 1.3%，DBP-2的r（2）= 2.0%，DBP-2的r（2）= 2.0%）。
Background: Vitamin D status, determined on the basis of 25-hydroxyvitamin D [25(OH) D] concentrations, is associated with the risk of several diseases. Vitamin D binding protein (DBP) is the major carrier of vitamin D and its metabolites, but the role of DBP single nucleotide polymorphisms (SNPs) on 25(OH) D concentrations is unclear.Objective: The objective was to evaluate the association of 2 DBP gene SNPs with 25(OH) D concentrations and explore whether such association varies according to the amount of vitamin D that needs to be transported.Design: This cross-sectional study included 741 premenopausal white women, mostly of French descent. Plasma 25(OH) D concentrations were measured by radioimmunoassay. DBP-1 (rs7041) and DBP-2 (rs4588) were genotyped with a Sequenom MassArray platform. Associations and interactions were modeled by using multivariate linear regression.Results: DBP-1 and DBP-2 SNPs were in strong linkage disequilibrium and were both associated with 25(OH) D concentrations. An additional copy of the rare allele of DBP-1 or DBP-2 was associated with lower 25(OH) D concentrations (beta = -3.29, P for trend = 0.0003; beta = -4.22, P for trend, = 0.0001, respectively). These DBP polymorphisms explained as much of the variation in circulating 25(OH) D as did total vitamin D intake (r(2) = 1.3% for DBP-1, r(2) = 2.0% for DBP-2, and r(2)