Evidence supports a role of host genetic diversity in the clinical course of coronavirus disease 2019 (COVID-19). Variation in the cannabinoid CB2 receptor gene (CNR2) could affect the regulatory action of endocannabinoids on the immune system, resulting in an increased risk of various inflammatory diseases. The present study investigated the relationship between the CNR2-Q63R variant and COVID-19 severity. A total of 200 Iranian COVID-19 patients were enrolled in the study and genotyped using a TaqMan assay. The co-dominant, dominant, recessive, over-dominant, and additive inheritance models were analyzed using SNPStats software. In silico molecular docking was also performed to simulate the effects of the Q63R variation on CB2 binding with a ligand and with the G-protein. A significant difference in the Q63R allele and genotype distribution was found between expired and discharged COVID-19 patients in co-dominant, recessive, and additive inheritance models. The molecular docking results showed that the predicted structure of mutant CB2 (63R type) could not bind to the G-protein in the correct position. The data indicated that the Q63R variation in the CNR2 gene may affect the severity of COVID-19. Identification of genes related to susceptibility and severity of COVID-19 may lead to specific targets for drug repurposing or development.

Graphic abstract

中文翻译：

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大麻素 CB2 受体的功能变异 (Q63R) 可能会影响 COVID-19 的严重程度：一项人体研究和分子对接

证据支持宿主遗传多样性在 2019 年冠状病毒病 (COVID-19) 临床过程中的作用。大麻素 CB2 受体基因 ( CNR2 ) 的变异可能会影响内源性大麻素对免疫系统的调节作用，从而导致各种炎症性疾病的风险增加。本研究调查了CNR2 -Q63R 变体与 COVID-19 严重程度之间的关系。共有 200 名伊朗 COVID-19 患者参加了该研究，并使用 TaqMan 分析进行了基因分型。使用 SNPStats 软件分析了共显性、显性、隐性、过度显性和加性遗传模型。计算机还进行了分子对接以模拟 Q63R 变异对 CB2 与配体和 G 蛋白结合的影响。在共显性、隐性和加性遗传模型中，Q63R 等位基因和基因型分布在过期和出院的 COVID-19 患者之间存在显着差异。分子对接结果表明突变CB2（63R型）的预测结构不能与正确位置的G蛋白结合。数据表明，CNR2 基因中的Q63R变异可能会影响 COVID-19 的严重程度。鉴定与 COVID-19 的易感性和严重性相关的基因可能会导致药物再利用或开发的特定目标。

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