Maiti Amit K
Department of Genetics, Mydnavar, 28475 Greenfield Rd, Southfield, MI 48076, USA.
Int J Mol Sci. 2025 Jul 11;26(14):6680. doi: 10.3390/ijms26146680.
Long- or post-COVID-19 syndrome, which is also designated by WHO as Post COVID-19 Condition (PCC), is characterized by the persistent symptoms that remain after recovery from SARS-CoV-2 infection. A worldwide consortium of Long COVID-19 Host Genetics Initiative (Long COVID-19 HGI) identified an SNP rs9367106 (G>C; chr6:41,515,652, GRCh38, = 1.76 × 10, OR = 1.63, 95% CI: 1.40-1.89) that is associated with PCC. Unraveling the functional significance of this SNP is of prime importance to understanding the development of the PCC phenotypes and their therapy. Here, in Silico, I explored how the risk allele of this SNP alters the functional mechanisms and molecular pathways leading to the development of PCC phenotypes. Bioinformatic methods include physical interactions using HI-C and Chia-PET analysis, Transcription Factors (TFs) binding ability, RNA structure modeling, epigenetic, and pathway analysis. This SNP resides within two long RNA genes, and , and is located at ~31 kb upstream of a transcription factor FOXP4. This DNA region, including this SNP, physically interacts with and , implying that this regulatory SNP could alter the normal cellular function of and . Furthermore, rs9367106 is in eQTL with the gene in lung tissue. rs9367106 carrying DNA sequences act as distant enhancers and bind with several transcription factors (TFs) including YY1, PPAR-α, IK-1, GR-α, and AP2αA. The G>C transition extensively modifies the RNA structure that may affect the TF bindings and enhancer functions to alter the interactions and functions of these RNA molecules. This SNP also includes an ALU/SINE sequence and alteration of which by the G>C transition may prevent /MDA5 activation, leading to suppression of host innate immune responses. targets the gene that expresses mostly in brain tissues, associated with sleep disorders and basal ganglia abnormalities similar to some of the symptoms of PCC phenotypes. Taken together, G>C transition of rs9367601 may likely alter the function of all three genes to explain the molecular basis of developing the long-term symptomatic abnormalities in the lungs and brain observed after COVID-19 recovery.
新冠后综合征，世界卫生组织（WHO）也将其指定为新冠后状况（PCC），其特征是在从SARS-CoV-2感染中恢复后仍持续存在的症状。一个全球性的新冠后宿主遗传学倡议联盟（Long COVID-19 HGI）确定了一个单核苷酸多态性（SNP）rs9367106（G>C；chr6:41,515,652，GRCh38， = 1.76 × 10，优势比（OR） = 1.63，95%置信区间：1.40 - 1.89），该SNP与PCC相关。阐明此SNP的功能意义对于理解PCC表型的发展及其治疗至关重要。在此，我通过计算机模拟，探究了该SNP的风险等位基因如何改变导致PCC表型发展的功能机制和分子途径。生物信息学方法包括使用Hi-C和Chia-PET分析的物理相互作用、转录因子（TFs）结合能力、RNA结构建模、表观遗传学和途径分析。此SNP位于两个长RNA基因 和 内，且位于转录因子FOXP4上游约31 kb处。包括此SNP在内 的这个DNA区域与 和 发生物理相互作用，这意味着这个调控SNP可能会改变 和 的正常细胞功能。此外，rs9367106在肺组织中与 基因处于表达数量性状位点（eQTL）关系。携带rs9367106的DNA序列充当远距离增强子，并与包括YY1、PPAR-α、IK-1、GR-α和AP2αA在内的多种转录因子（TFs）结合。G>C转换广泛修饰了RNA结构，这可能会影响TF结合和增强子功能，从而改变这些RNA分子的相互作用和功能。此SNP还包含一个ALU/SINE序列，G>C转换对其的改变可能会阻止 /MDA5激活，导致宿主先天免疫反应受到抑制。 靶向主要在脑组织中表达的 基因，该基因与睡眠障碍和基底神经节异常有关，类似于PCC表型的一些症状。综上所述，rs9367601的G>C转换可能会改变这三个基因的功能，从而解释新冠恢复后在肺部和脑部观察到的长期症状性异常发展的分子基础。
