Genetic and environmental influences on plasma vitamin D binding protein concentrations.
Genetic and environmental influences on plasma vitamin D binding protein concentrations.
复制标题
遗传和环境对血浆维生素 D 结合蛋白浓度的影响。
DOI：
10.1016/j.trsl.2014.08.003
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
El-Bayoumy,Karam
中科院分区：
文献类型：
--
作者：
Wilson,RobinTaylor;BortnerJr,JamesD;Roff,Alanna;Das,Arunangshu;Battaglioli,EricJ;RichieJr,JohnP;Barnholtz-Sloan,Jill;Chinchilli,VernonM;Berg,Arthur;Liu,Guodong;Salzberg,AnnaC;El-Bayoumy,Karam
最近的研究表明，低维生素 D 结合蛋白（VDBP，又名群体特异性补体或 Gc）浓度可能与炎症介导的疾病有关，包括哮喘、慢性阻塞性肺病和癌症。然而，这些研究可能会因种族和民族或基因的巨大差异而混淆。本研究的目的是检验循环 VDBP 浓度与遗传血统显着相关的假设。我们使用经过验证的高效液相色谱串联质谱法测定 25-羟基维生素 D3 及其下游代谢物 24,25-二羟基维生素 D3。使用商业酶联免疫吸附测定法在健康的非洲裔美国人 (n = 56) 和白种人美国人 (n = 60) 参与者中重复测量 VDBP 浓度（毫克/升）。整个基因组的祖先信息标记被用来估计个体遗传祖先比例，旨在强有力地区分西非和欧洲血统。基因型定义的 Gc 亚型是使用 rs7041 和 rs4588 组合组定义的。 VDBP 浓度与 Gc 异构体 (r= 0.93，P< 0.001) 和西非遗传血统 (r= -0.66，P< 0.001) 相关。在最终模型中，在调整遗传血统后，Gc 亚型、血清维生素 D 的分解代谢比、口服避孕药的使用和体重指数仍然与 VDBP 浓度显着相关。未能调整 Gc 同工型可能会导致 VDBP 浓度和疾病风险研究中出现虚假关联，特别是当目标病症也可能与遗传血统相关时。这里观察到的白种美国人中较高的循环 VDBP 浓度和较高的维生素 D 分解代谢率似乎与较低的骨矿物质密度以及维生素 D 诱导细胞因子的种族和民族差异一致。
Recent studies suggest that low vitamin D–binding protein (VDBP aka group-specific complement or Gc) concentrations may be linked with inflammatory-mediated conditions, including asthma, chronic obstructive pulmonary disease, and cancer. However, these studies may be confounded by substantial racial and ethnic or genetic differences. The purpose of this study was to test the hypothesis that circulating VDBP concentrations are significantly associated with genetic ancestry. We used a validated high-performance liquid chromatography tandem mass spectrometry assay of 25-hydroxyvitamin D3and its downstream metabolite 24,25-dihydroxyvitamin D3. VDBP concentrations (milligrams per liter) were measured in duplicate using a commercial enzyme-linked immunosorbent assay among healthy African American (n = 56) and Caucasian American (n = 60) participants. Ancestry informative markers across the genome were used to estimate individual genetic ancestry proportions, designed to robustly distinguish between West African and European ancestry. Genotype-defined Gc isoforms were defined using rs7041 and rs4588 combination groups. VDBP concentration was correlated with both Gc isoform (r= 0.93,P< 0.001) and West African genetic ancestry (r= −0.66,P< 0.001). In the final model, Gc isoform, the catabolic ratio of serum vitamin D, oral contraceptive use, and body mass index remained significantly associated with VDBP concentration, after adjustment for genetic ancestry. Failure to adjust for Gc isoform may lead to spurious associations in studies of VDBP concentration and disease risk, particularly when the condition of interest may also be associated with genetic ancestry. The higher circulating VDBP concentrations and higher vitamin D catabolic rate among Caucasian Americans observed here appear to be consistent with lower bone mineral density and racial and ethnic differences in vitamin D–inducing cytokines.