Aslan Elif Sibel, White Kenneth, Meral Gulsen, Akcay Zeyneb Nur, Altundag Aytug, Gur Savas, Dokur Mehmet, Baktir Mehmet Akif, Karcioglu Batur Lutfiye
Department of Molecular Biology and Genetics, Biruni University, Merkezefendi, 75 Sk No:1-13 M.G., 34015 Istanbul, Turkey.
Biruni University Research Center (B@MER), Biruni University, 34015 Istanbul, Turkey.
Diagnostics (Basel). 2024 Dec 15;14(24):2823. doi: 10.3390/diagnostics14242823.
BACKGROUND/AIM: Loss of smell, also known as anosmia, is a prevalent and often prolonged symptom following infection with SARS-CoV-2. While many patients regain olfactory function within weeks, a significant portion experience persistent anosmia lasting over a year post-infection. The underlying mechanisms responsible for this sensory deficit remain largely uncharacterized. Previous studies, including genome-wide association studies (GWAS), have identified genetic variants near the UGT2A1 and UGT2A2 genes that are linked to anosmia in COVID-19 patients. However, the role of epigenetic changes in the development and persistence of smell loss has not been well explored. In this study, we aimed to investigate epigenetic alterations in the form of DNA methylation in the UGT1A1 gene, which is a locus associated with olfactory dysfunction in COVID-19 patients.
We analysed DNA methylation patterns in blood samples from two carefully matched cohorts of 20 COVID-19 patients each, which are differentiated by their olfactory function-those with normal smell (normosmia) and those suffering from smell loss (anosmia). The cohorts were matched for age and sex to minimize potential confounding factors.
Using quantitative analysis, we found significantly lower levels of DNA methylation in the UGT1A1 locus in the anosmia group compared to the normosmia group, with a 14% decrease in median methylation values in patients with smell loss ( < 0.0001). These findings highlight potential epigenomic alterations in the UGT1A1 gene that may contribute to the pathogenesis of anosmia following COVID-19 infection. Our results suggest that the methylation status at this locus could serve as a biomarker for olfactory dysfunction in affected individuals.
This study is among the first to describe epigenetic changes associated with smell loss in COVID-19, providing a foundation for future research into targeted interventions and potential therapeutic strategies aimed at reversing persistent anosmia. Further investigations involving larger cohorts and additional loci may help elucidate the complex interaction between genetic, epigenetic, and environmental factors influencing long-term sensory impairment post-COVID-19.
背景/目的：嗅觉丧失，也称为嗅觉缺失，是感染新型冠状病毒后一种普遍且往往持续时间较长的症状。虽然许多患者在数周内恢复嗅觉功能，但仍有相当一部分患者在感染后一年多仍持续存在嗅觉缺失。导致这种感觉缺陷的潜在机制在很大程度上仍未明确。包括全基因组关联研究（GWAS）在内的先前研究已经确定了UGT2A1和UGT2A2基因附近的基因变异与新冠病毒感染患者的嗅觉缺失有关。然而，表观遗传变化在嗅觉丧失的发生和持续中的作用尚未得到充分研究。在本研究中，我们旨在研究UGT1A1基因中DNA甲基化形式的表观遗传改变，该基因是与新冠病毒感染患者嗅觉功能障碍相关的一个位点。
我们分析了来自两个精心匹配的队列的血液样本中的DNA甲基化模式，每个队列有20名新冠病毒感染患者，根据嗅觉功能分为嗅觉正常（嗅觉正常）和嗅觉丧失（嗅觉缺失）两组。队列在年龄和性别上进行了匹配，以尽量减少潜在的混杂因素。
通过定量分析，我们发现嗅觉缺失组中UGT1A1位点的DNA甲基化水平明显低于嗅觉正常组，嗅觉丧失患者的甲基化中位数降低了14%（<0.0001）。这些发现突出了UGT1A1基因中潜在的表观基因组改变，这些改变可能导致新冠病毒感染后嗅觉缺失的发病机制。我们的结果表明，该位点的甲基化状态可作为受影响个体嗅觉功能障碍的生物标志物。
本研究是最早描述与新冠病毒感染嗅觉丧失相关的表观遗传变化的研究之一，为未来针对逆转持续性嗅觉缺失的靶向干预和潜在治疗策略的研究奠定了基础。涉及更大队列和更多位点的进一步研究可能有助于阐明影响新冠病毒感染后长期感觉障碍的遗传、表观遗传和环境因素之间的复杂相互作用。
