关键词: ATP P2X7 receptor COVID-19 SARS-CoV-2 adenosine A2A receptor polymorphisms

Mesh : Humans Male Middle Aged Aged Aged, 80 and over Polymorphism, Single Nucleotide Receptors, Purinergic P2X7 / genetics metabolism Receptor, Adenosine A2A / genetics Patient Acuity COVID-19 / complications genetics pathology Genotype Gene Frequency Cardiovascular Diseases / complications genetics Colonic Neoplasms / complications genetics

来  源:   DOI:10.3390/ijms25116135   PDF(Pubmed)

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:
SARS-CoV-2感染范围从轻度到重度,根据异常炎症反应的强度。嘌呤能受体双重控制炎症反应:而腺苷A2A受体(A2ARs)是抗炎的,ATPP2X7受体(P2X7Rs)发挥促炎作用。这项研究的目的是评估ADORA2A的功能丧失SNP(rs2298383)和P2RX7的功能获得单核苷酸多态性(SNP)的等位基因和基因型频率是否存在差异(rs208294)在SARS-CoV-2相关感染的严重程度。纳入55人,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两种SNP。TT基因型(与CT+CC)和T等位基因(vs.发现P2RX7SNP的C等位基因)与更严重形式的COVID-19有关,而ADORA2ASNP与感染严重程度之间的关联没有显着差异。P2RX7SNP的T等位基因在患有一种以上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。我们的发现表明P2X7R而不是A2AR多态性在SARS-CoV-2感染中的作用更加突出。尽管应该进行更大规模的基于人群的研究来验证我们的结论.
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