Uitterlinden André G, Fang Yue, Van Meurs Joyce B J, Pols Huibert A P, Van Leeuwen Johannes P T M
Genetic Laboratory, Room Ee575, Department of Internal Medicine, Erasmus MC, Dr. Molewaterplein 50, PO Box 1738, NL-3000 DR Rotterdam, The Netherlands.
Gene. 2004 Sep 1;338(2):143-56. doi: 10.1016/j.gene.2004.05.014.
The vitamin D endocrine system is involved in a wide variety of biological processes including bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation. Variations in this endocrine system have, thus, been linked to several common diseases, including osteoarthritis (OA), diabetes, cancer, cardiovascular disease, and tuberculosis. Evidence to support this pleiotropic character of vitamin D has included epidemiological studies on circulating vitamin D hormone levels, but also genetic epidemiological studies. Genetic studies provide excellent opportunities to link molecular insights with epidemiological data and have therefore gained much interest. DNA sequence variations, which occur frequently in the population, are referred to as "polymorphisms" and can have modest and subtle but true biological effects. Their abundance in the human genome as well as their high frequencies in the human population have made them targets to explain variation in risk of common diseases. Recent studies have indicated many polymorphisms to exist in the vitamin D receptor (VDR) gene, but the influence of VDR gene polymorphisms on VDR protein function and signaling is largely unknown. So far, three adjacent restriction fragment length polymorphisms for BsmI, ApaI, and TaqI, respectively, at the 3' end of the VDR gene have been the most frequently studied. Because these polymorphisms are probably nonfunctional, linkage disequilibrium with one or more truly functional polymorphisms elsewhere in the VDR gene is assumed to explain the associations observed. Research is therefore focussed on documenting additional polymorphisms across the VDR gene to verify this hypothesis and on trying to understand the functional consequences of the variations. Substantial progress has been made that will deepen our understanding of variability in the vitamin D endocrine system and might find applications in risk assessment of disease and in predicting response-to-treatment.
维生素D内分泌系统参与多种生物过程，包括骨代谢、免疫反应调节以及细胞增殖与分化的调控。因此，该内分泌系统的变异与多种常见疾病相关，包括骨关节炎（OA）、糖尿病、癌症、心血管疾病和结核病。支持维生素D这种多效性特征的证据不仅包括关于循环维生素D激素水平的流行病学研究，还包括遗传流行病学研究。遗传研究为将分子见解与流行病学数据联系起来提供了绝佳机会，因此备受关注。DNA序列变异在人群中频繁出现，被称为“多态性”，可能具有适度且微妙但真实的生物学效应。它们在人类基因组中的丰富性以及在人群中的高频率使其成为解释常见疾病风险变异的目标。最近的研究表明维生素D受体（VDR）基因存在许多多态性，但VDR基因多态性对VDR蛋白功能和信号传导的影响在很大程度上尚不清楚。到目前为止，VDR基因3'端分别针对BsmI、ApaI和TaqI的三个相邻限制性片段长度多态性是研究最频繁的。由于这些多态性可能无功能，因此假定与VDR基因其他位置的一个或多个真正有功能的多态性存在连锁不平衡来解释所观察到的关联。因此，研究重点在于记录VDR基因上更多的多态性以验证这一假设，并试图了解这些变异的功能后果。已经取得了实质性进展，这将加深我们对维生素D内分泌系统变异性的理解，并可能在疾病风险评估和预测治疗反应方面找到应用。
