Li Jiang, Tiwari Anshul, Mirzakhani Hooman, Wang Alberta L, Kho Alvin T, McGeachie Michael J, Litonjua Augusto A, Weiss Scott T, Tantisira Kelan G
Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, China.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Pers Med. 2021 Apr 16;11(4):307. doi: 10.3390/jpm11040307.
Of children with recurrent wheezing in early childhood, approximately half go on to develop asthma. MicroRNAs have been described as excellent non-invasive biomarkers due to their prognostic utility. We hypothesized that circulating microRNAs can predict incident asthma and that that prediction might be modified by vitamin D. We selected 75 participants with recurrent wheezing at 3 years old from the Vitamin D Antenatal Asthma Reduction Trial (VDAART). Plasma samples were collected at age 3 and sequenced for small RNA-Seq. The read counts were normalized and filtered by depth and coverage. Logistic regression was employed to associate miRNAs at age 3 with asthma status at age 5. While the overall effect of miRNA on asthma occurrence was weak, we identified 38 miRNAs with a significant interaction effect with vitamin D and 32 miRNAs with a significant main effect in the high vitamin D treatment group in VDAART. We validated the VDAART results in Project Viva for both the main effect and interaction effect. Meta-analysis was performed on both cohorts to obtain the combined effect and a logistic regression model was used to predict incident asthma at age 7 in Project Viva. Of the 23 overlapped miRNAs in the stratified and interaction analysis above, 9 miRNAs were replicated in Project Viva with strong effect size and remained in the meta-analysis of the two populations. The target genes of the 9 miRNAs were enriched for asthma-related Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. Using logistic regression, microRNA hsa-miR-574-5p had a good prognostic ability for incident asthma prognosis with an area under the receiver operating characteristic (AUROC) of 0.83. In conclusion, miRNAs appear to be good biomarkers of incident asthma, but only when vitamin D level is considered.
在幼儿期反复喘息的儿童中，约有一半会发展为哮喘。微小RNA因其预后效用而被描述为优秀的非侵入性生物标志物。我们假设循环微小RNA可以预测哮喘的发生，并且这种预测可能会受到维生素D的影响。我们从维生素D产前哮喘减少试验（VDAART）中选取了75名3岁时反复喘息的参与者。在3岁时采集血浆样本并进行小RNA测序。读取计数通过深度和覆盖度进行归一化和过滤。采用逻辑回归分析3岁时的微小RNA与5岁时的哮喘状态之间的关联。虽然微小RNA对哮喘发生的总体影响较弱，但我们在VDAART的高维生素D治疗组中鉴定出38种与维生素D有显著相互作用效应的微小RNA和32种有显著主效应的微小RNA。我们在“活力计划”中验证了VDAART关于主效应和相互作用效应的结果。对两个队列进行荟萃分析以获得合并效应，并使用逻辑回归模型预测“活力计划”中7岁时哮喘的发生。在上述分层和相互作用分析中重叠的23种微小RNA中，有9种在“活力计划”中得到复制，效应大小较强，并保留在两个人群的荟萃分析中。这9种微小RNA的靶基因在与哮喘相关的京都基因与基因组百科全书（KEGG）信号通路中富集。使用逻辑回归分析，微小RNA hsa-miR-574-5p对哮喘发生预后具有良好的预测能力，受试者工作特征曲线下面积（AUROC）为0.83。总之，微小RNA似乎是哮喘发生的良好生物标志物，但前提是要考虑维生素D水平。
