Sharif-Zak Mohsen, Abbasi-Jorjandi Mojtaba, Asadikaram Gholamreza, Ghoreshi Zohreh-Al-Sadat, Rezazadeh-Jabalbarzi Mitra, Rashidinejad Hamidreza
Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran.
Department of Clinical Biochemistry, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
Iran J Sci Technol Trans A Sci. 2022;46(5):1309-1316. doi: 10.1007/s40995-022-01334-1. Epub 2022 Jul 27.
In the pathophysiology of COVID-19, immunomodulatory factors play a vital role. Viruses have epigenetic effects on various genes, particularly methylation. Explaining the changes in immunological factor methylation levels during viral infections requires substantial consideration. HLA-C is a crucial determinant of immune function and NK cell activity and is primarily implicated in viral infections. This research focused on studying HLA-C methylation in COVID-19 patients with different severity. Peripheral blood samples were collected from 470 patients (235 men and 235 women) with RT-qPCR-confirmed COVID-19 test and classified into moderate, severe, and critical groups based on WHO criteria. Also, one hundred (50 men and 50 women) healthy subjects were selected as the control group. Peripheral blood mononuclear cells were used for DNA extraction, and the methylation-specific PCR (MSP) method and gel electrophoresis were used to determine the methylation status of the HLA-C. Significant statistical differences in HLA-C methylation were observed among cases and controls and various stages of the disease. HLA-C methylation in men and women has decreased in all stages ( < 0.05). In comparison with control, HLA-C methylation in both genders were as follows: moderate (women: 41.0%, men: 52.33%), severe (women: 43.42%, men: 64.86%), critical (women: 42.33%, men: 60.07%), and total patients (women: 45.52%, men: 56.97%). Furthermore, the methylation levels in men were higher than in women in all groups ( < 0.05). Significantly, among all groups, the severe group of men participants showed the highest methylation percentage ( < 0.05). No significant differences were detected for different disease severity in the women group ( > 0.1). This study found that HLA-C methylation was significantly lower in COVID-19 patients with different disease severity. There were also significant differences in HLA-C methylation between men and women patients with different severity. Therefore, during managing viral infections, particularly COVID-19, it is critical to consider patient gender and disease severity.
在新冠病毒疾病（COVID-19）的病理生理学中，免疫调节因子起着至关重要的作用。病毒对各种基因具有表观遗传效应，尤其是甲基化。解释病毒感染期间免疫因子甲基化水平的变化需要充分考虑。人类白细胞抗原C（HLA-C）是免疫功能和自然杀伤细胞活性的关键决定因素，主要与病毒感染有关。本研究聚焦于不同严重程度的COVID-19患者的HLA-C甲基化情况。从470例经逆转录定量聚合酶链反应（RT-qPCR）确诊为COVID-19的患者（235名男性和235名女性）中采集外周血样本，并根据世界卫生组织标准分为中度、重度和危重组。此外，选取100名（50名男性和50名女性）健康受试者作为对照组。使用外周血单个核细胞进行DNA提取，并采用甲基化特异性聚合酶链反应（MSP）方法和凝胶电泳来确定HLA-C的甲基化状态。在病例组与对照组以及疾病的各个阶段之间，观察到HLA-C甲基化存在显著的统计学差异。男性和女性在所有阶段的HLA-C甲基化均有所下降（P＜0.05）。与对照组相比，不同性别患者的HLA-C甲基化情况如下：中度（女性：41.0%，男性：52.33%）、重度（女性：43.42%，男性：64.86%）、危重型（女性：42.33%，男性：60.07%）以及所有患者（女性：45.52%，男性：56.97%）。此外，所有组中男性的甲基化水平均高于女性（P＜0.05）。值得注意的是，在所有组中，男性重度组的甲基化百分比最高（P＜0.05）。在女性组中，不同疾病严重程度之间未检测到显著差异（P＞0.1）。本研究发现，不同疾病严重程度的COVID-19患者的HLA-C甲基化显著降低。不同严重程度的男性和女性患者之间的HLA-C甲基化也存在显著差异。因此，在处理病毒感染，尤其是COVID-19时，考虑患者性别和疾病严重程度至关重要。
