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P2RX7 基因多态性而非 ADORA2A 与 SARS-CoV-2 感染的严重程度相关。

Genetic Polymorphisms of P2RX7 but Not of ADORA2A Are Associated with the Severity of SARS-CoV-2 Infection.

机构信息

FMUC-Faculty of Medicine, University Coimbra, 3004-504 Coimbra, Portugal.

CNC-UC-Center for Neuroscience and Cell Biology, University Coimbra, 3004-504 Coimbra, Portugal.

出版信息

Int J Mol Sci. 2024 Jun 2;25(11):6135. doi: 10.3390/ijms25116135.

Abstract

SARS-CoV-2 infection ranges from mild to severe presentations, according to the intensity of the aberrant inflammatory response. Purinergic receptors dually control the inflammatory response: while adenosine A2A receptors (A2ARs) are anti-inflammatory, ATP P2X7 receptors (P2X7Rs) exert pro-inflammatory effects. The aim of this study was to assess if there were differences in allelic and genotypic frequencies of a loss-of-function SNP of ADORA2A (rs2298383) and a gain-of-function single nucleotide polymorphism (SNP) of P2RX7 (rs208294) in the severity of SARS-CoV-2-associated infection. Fifty-five individuals were enrolled and categorized according to the severity of the infection. Endpoint genotyping was performed in blood cells to screen for both SNPs. The TT genotype (vs. CT + CC) and the T allele (vs. C allele) of P2RX7 SNP were found to be associated with more severe forms of COVID-19, whereas the association between ADORA2A SNP and the severity of infection was not significantly different. The T allele of P2RX7 SNP was more frequent in people with more than one comorbidity and with cardiovascular conditions and was associated with colorectal cancer. Our findings suggest a more prominent role of P2X7R rather than of A2AR polymorphisms in SARS-CoV-2 infection, although larger population-based studies should be performed to validate our conclusions.

摘要

根据异常炎症反应的强度,SARS-CoV-2 感染的表现从轻症到重症不等。嘌呤能受体双重控制炎症反应:腺苷 A2A 受体 (A2AR) 具有抗炎作用,而 ATP P2X7 受体 (P2X7R) 则具有促炎作用。本研究旨在评估 ADORA2A(rs2298383)的功能丧失 SNP 和 P2RX7(rs208294)的单核苷酸多态性(SNP)的等位基因和基因型频率在 SARS-CoV-2 相关感染严重程度上是否存在差异。共纳入 55 名个体,并根据感染的严重程度进行分类。在血细胞中进行终点基因分型以筛选这两个 SNP。发现 P2RX7 SNP 的 TT 基因型(与 CT + CC 相比)和 T 等位基因(与 C 等位基因相比)与更严重的 COVID-19 形式相关,而 ADORA2A SNP 与感染严重程度之间的关联没有显著差异。P2RX7 SNP 的 T 等位基因在患有多种合并症和心血管疾病的人群中更为常见,并且与结直肠癌相关。我们的研究结果表明,P2X7R 而不是 A2AR 多态性在 SARS-CoV-2 感染中起更重要的作用,尽管应进行更大的基于人群的研究来验证我们的结论。

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