Department of Pathology, University of Florida, Gainesville, Florida, USA.
Diabetes. 2011 Oct;60(10):2566-70. doi: 10.2337/db11-0576. Epub 2011 Aug 15.
Previous studies have noted a specific association between type 1 diabetes and insufficient levels of vitamin D, as well as polymorphisms within genes related to vitamin D pathways. Here, we examined whether serum levels or genotypes of the vitamin D-binding protein (VDBP), a molecule key to the biologic actions of vitamin D, specifically associate with the disorder.
A retrospective, cross-sectional analysis of VDBP levels used samples from 472 individuals of similar age and sex distribution, including 153 control subjects, 203 patients with type 1 diabetes, and 116 first-degree relatives of type 1 diabetic patients. Single nucleotide polymorphism (SNP) typing for VDBP polymorphisms (SNP rs4588 and rs7041) was performed on this cohort to determine potential genetic correlations. In addition, SNP analysis of a second sample set of banked DNA samples from 1,502 type 1 diabetic patients and 1,880 control subjects also was used to determine genotype frequencies.
Serum VDBP levels were highest in healthy control subjects (median 423.5 µg/mL [range 193.5-4,345.0; interquartile range 354.1-]586), intermediate in first-degree relatives (402.9 µg/mL [204.7-4,850.0; 329.6-492.4]), and lowest in type 1 diabetic patients (385.3 µg/mL [99.3-1,305.0; 328.3-473.0]; P = 0.003 vs. control subjects). VDBP levels did not associate with serum vitamin D levels, age, or disease duration. However, VDBP levels were, overall, lower in male subjects (374.7 µg/mL [188.9-1,602.0; 326.9-449.9]) than female subjects (433.4 µg/mL [99.3-4,850.0; 359.4-567.8]; P < 0.0001). It is noteworthy that no differences in genotype frequencies of the VDBP polymorphisms were associated with serum VDBP levels or between type 1 diabetic patients and control subjects.
Serum VDBP levels are decreased in those with type 1 diabetes. These studies suggest that multiple components in the metabolic pathway of vitamin D may be altered in type 1 diabetes and, collectively, have the potential to influence disease pathogenesis.
先前的研究已经注意到 1 型糖尿病与维生素 D 水平不足以及与维生素 D 途径相关基因的多态性之间存在特定关联。在这里，我们研究了维生素 D 结合蛋白（VDBP）的血清水平或基因型是否与该疾病有特定关联，VDBP 是维生素 D 生物学作用的关键分子。
对来自 472 名年龄和性别分布相似的个体的 VDBP 水平进行回顾性、横断面分析，包括 153 名对照受试者、203 名 1 型糖尿病患者和 116 名 1 型糖尿病患者的一级亲属。对该队列进行 VDBP 多态性（SNP rs4588 和 rs7041）的单核苷酸多态性（SNP）分型，以确定潜在的遗传相关性。此外，还使用来自 1502 名 1 型糖尿病患者和 1880 名对照受试者的银行储存 DNA 样本的 SNP 分析来确定基因型频率。
健康对照受试者的血清 VDBP 水平最高（中位数 423.5 µg/mL [范围 193.5-4345.0；四分位距 354.1-586]），一级亲属为 402.9 µg/mL [204.7-4850.0；329.6-492.4]），1 型糖尿病患者最低（385.3 µg/mL [99.3-1305.0；328.3-473.0]；P = 0.003 与对照组相比）。VDBP 水平与血清维生素 D 水平、年龄或疾病持续时间无关。然而，总体而言，男性受试者的 VDBP 水平（374.7 µg/mL [188.9-1602.0；326.9-449.9]）低于女性受试者（433.4 µg/mL [99.3-4850.0；359.4-567.8]；P < 0.0001）。值得注意的是，VDBP 多态性的基因型频率与血清 VDBP 水平或 1 型糖尿病患者与对照组之间没有差异。
1 型糖尿病患者的血清 VDBP 水平降低。这些研究表明，1 型糖尿病中维生素 D 代谢途径的多个成分可能发生改变，并且它们共同具有影响疾病发病机制的潜力。
