Polymorphisms in the Vitamin D System and Health, 2013

Vitamin D is produced in the skin after sun exposure or obtained from food, mainly fatty fish or vitamin D supplements. For activation vitamin D must be hydroxylated in the liver to 25(OH)D and thereafter in the kidney to 1,25(OH)2D. For 1,25(OH)2D to exert its effect it has to bind to the vitamin D receptor (VDR). The serum level of 25(OH)D is in part genetically determined and several polymorphisms with effects on serum 25(OH)D have been identified. These polymorphisms appear as important for the serum 25(OH)D level as the effect of season, or vitamin D supplementation. Vitamin D is not only vital for the skeleton, but appears also to be related to heart disease, diabetes, cancer and mortality. However, as the serum level of 25(OH)D is strongly influenced by lifestyle factors that are also related to health outcomes, it is difficult to decide whether the relation between vitamin D and health is causal or not. On the other hand, the polymorphisms are not influenced by life-style, and the effect of the polymorphisms will be life-long. Accordingly, they may be a better marker of vitamin D status than a single serum 25(OH)D measurement. Furthermore, there are a number of polymorphisms regarding the VDR that may be associated with health. In the Tromsø study DNA is available from almost 27,000 individuals, and end-point registers have been made for fractures, coronary infarction, diabetes, cancer and mortality. In the present study we therefore related the polymorphisms affecting the serum 25(OH)D level and the function of the VDR with these endpoints with the use of a case-cohort design. If we were to find the expected associations between the polymorphisms and diseases, this would further strengthen the role of vitamin D in human health, and may have importance for recommendations regarding vitamin D supplementation. Considering the high prevalence of vitamin D deficiency worldwide, this could potentially have huge consequences for public health.

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维生素D可经日晒后在皮肤中合成，亦可从食物（主要为高脂鱼类）及维生素D补充剂中获取。维生素D需先在肝脏中羟化为25(OH)D，随后在肾脏中进一步羟化为1,25(OH)₂D方能被激活。1,25(OH)₂D发挥生物学效应需结合维生素D受体（Vitamin D Receptor, VDR）。
血清25(OH)D水平部分由遗传因素决定，目前已鉴定出多种可影响血清25(OH)D水平的基因多态性。此类多态性对血清25(OH)D水平的影响程度，与季节或维生素D补充的效应相当。
维生素D不仅对骨骼健康至关重要，还被发现与心脏病、糖尿病、癌症及全因死亡率存在关联。然而，由于血清25(OH)D水平极易受与健康结局相关的生活方式因素影响，因此难以明确维生素D与健康之间的关联是否为因果关系。
与之相对，基因多态性不受生活方式因素影响，且其效应终身存在。因此，相较于单次血清25(OH)D检测结果，基因多态性或许可作为更优的维生素D营养状态标志物。
此外，与VDR相关的多种基因多态性可能与健康状况相关。
特罗姆瑟研究（Tromsø Study）获取了近27000名个体的DNA样本，并建立了骨折、心肌梗死、糖尿病、癌症及全因死亡率的终点登记库。本研究因此采用病例队列研究设计，分析影响血清25(OH)D水平的基因多态性及VDR功能多态性与上述终点事件的关联。
若能验证预期的基因多态性与疾病间的关联，将进一步佐证维生素D在人类健康中的核心作用，并可能对维生素D补充的临床推荐方案产生重要指导意义。鉴于全球范围内维生素D缺乏的高患病率，该研究结果或对公共卫生产生深远影响。
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