Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Va.
Department of Biochemistry and Molecular Biology and the Massey Cancer Center, Virginia Commonwealth University School of Medicine, Richmond, Va.
J Allergy Clin Immunol. 2019 Sep;144(3):634-640. doi: 10.1016/j.jaci.2019.07.023. Epub 2019 Jul 31.
There is a strong genetic component to asthma, and numerous genome-wide association studies have identified ORM1 (yeast)-like protein 3 (ORMDL3) as a gene associated with asthma susceptibility. However, how ORMDL3 contributes to asthma pathogenesis and its physiologic functions is not well understood and a matter of great debate. This rostrum describes recent advances and new insights in understanding of the multifaceted functions of ORMDL3 in patients with allergic asthma. We also suggest a potential unifying paradigm and discuss molecular mechanisms for the pathologic functions of ORMDL3 in asthma related to its evolutionarily conserved role in regulation of sphingolipid homeostasis. Finally, we briefly survey the utility of sphingolipid metabolites as potential biomarkers for allergic asthma.
哮喘有很强的遗传因素，许多全基因组关联研究已经确定 ORM1（酵母）样蛋白 3（ORMDL3）是与哮喘易感性相关的基因。然而，ORMDL3 如何导致哮喘发病机制及其生理功能尚不清楚，这是一个争论的焦点。本专题描述了在理解变应性哮喘患者 ORMDL3 的多方面功能方面的最新进展和新见解。我们还提出了一个潜在的统一范式，并讨论了 ORMDL3 在哮喘中的病理功能的分子机制，这与其在调节鞘脂类稳态方面的进化保守作用有关。最后，我们简要调查了鞘脂代谢物作为潜在的变应性哮喘生物标志物的用途。
