Vitamins D 2 and D 3 have overlapping but different effects on human gene expression revealed through analysis of blood transcriptomes in a randomised double-blind placebo-controlled food-fortification trial
Vitamins D 2 and D 3 have overlapping but different effects on human gene expression revealed through analysis of blood transcriptomes in a randomised double-blind placebo-controlled food-fortification trial
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一项随机双盲安慰剂对照食品强化试验中的血液转录组分析显示，维生素 D 2 和 D 3 对人类基因表达具有重叠但不同的影响
DOI：
10.1101/2020.12.16.20247700
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Durrant L
中科院分区：
文献类型：
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作者：
Durrant L
我们首次报道了维生素D2和维生素D3对代表两个种族（白色欧洲人和南亚人）的健康女性全血全基因组基因表达的影响。在这项随机安慰剂对照试验中，参与者每天给予生理剂量（15 μg）的维生素D2或D3，持续12周，并将转录组的变化与基线时的转录组进行比较。虽然在补充每种维生素D来源后差异表达基因的库中存在一些重叠，但大多数变化都是针对维生素D3或维生素D2的，这表明每种形式的维生素可能对人体生理学有不同的影响。值得注意的是，补充维生素D3后，大多数基因表达的变化反映了基因活性的下调，这些基因是先天性和适应性免疫系统的许多编码成分。这些与维生素D协调免疫系统向更耐受性状态转变的新兴概念一致。此外，在补充维生素D3或维生素D2后，观察到与1型和2型干扰素活性相关的基因表达的不同变化。这是特别有趣的，因为干扰素在对感染的先天反应中发挥关键作用，并且异常的1型干扰素信号传导与严重的COVID-19疾病有关。与维生素D3相比，在补充维生素D2后观察到的基因表达差异保证了对两种形式的维生素D对人体生理学的生物学效应的更深入的研究。显著性声明本研究表明维生素D2和D3对人体生理学的影响可能不一样，从全血中基因表达的差异推断。南亚参与者被发现在转录组水平上对维生素D补充剂的反应与白色欧洲人不同。本研究中鉴定的差异表达的免疫途径与维生素D协调更耐受性的免疫状态一致，这可能与对病毒感染（如Covid-19）的免疫应答的严重程度有关。我们观察到维生素D3增强1型干扰素信号传导，而不是维生素D2。
For the first time, we report the influence of vitamin D2and vitamin D3on genome-wide gene expression in whole blood from healthy women representing two ethnic groups, white European and South Asian. In this randomised placebo-controlled trial, participants were given daily physiological doses (15 µg) of either vitamin D2or D3for 12 weeks and changes in the transcriptome were compared relative to the transcriptome at baseline. While there was some overlap in the repertoire of differentially expressed genes after supplementation with each vitamin D source, most changes were specific to either vitamin D3or vitamin D2, suggesting that each form of the vitamin may have different effects on human physiology. Notably, following vitamin D3supplementation, the majority of changes in gene expression reflected a down-regulation in the activity of genes, many encoding components of the innate and adaptive immune systems. These are consistent with the emerging concept that vitamin D orchestrates a shift in the immune system towards a more tolerogenic status. Moreover, divergent changes were observed following supplementation with either vitamin D3or vitamin D2for gene expression associated with type 1 and type 2 interferon activity. This is particularly intriguing as interferons play a critical role in the innate response to infection and aberrant type 1 interferon signalling is implicated in severe COVID-19 disease. The observed differences in gene expression after supplementation with vitamin D2compared with vitamin D3warrant a more intensive investigation of the biological effects of the two forms of vitamin D on human physiology.Significance statementsThis study suggests that the influence of vitamins D2and D3on human physiology may not be the same, as deduced from differences in gene expression within whole blood.South Asian participants were found to respond differently to vitamin D supplementation at the transcriptome level from white Europeans.The differentially expressed immune pathways identified in this study are consistent with vitamin D orchestrating a more tolerogenic immune status and this could be relevant in the context of the severity of immune response to viral infections such as Covid-19.The potential relevance of this study to severe Covid-19 disease is highlighted by our observed enhancement of type 1 interferon signalling by vitamin D3, but not vitamin D2.