Alyami Ahmed, Barnawi Fawziya B, Christmas Steve, Alyafee Yusra, Awadalla Maaweya, Al-Bayati Zaid, Alshehri Ahmad A, Saif Ahmed M, Mansour Lamjed
Pathology and Clinical Laboratory Medicine Administration, King Fahad Medical City, Riyadh Second Health Cluster, Riyadh, Saudi Arabia.
Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK.
Biochem Genet. 2024 Nov 4. doi: 10.1007/s10528-024-10951-x.
The objective of this study is to investigate the the relationships between HLA-G gene variants and sHLA-G with susceptibility to SARS-CoV-2 infection. In this case-control study, 65 Patients with COVID-19 were and 67 healthy controls were genotyped for their main functional polymorphisms namely, the 14-bp Ins/Del (rs371194629), +3003C/T (rs1707), +3010C/G (rs1710), +3027A/C (rs17179101), +3035C/T (rs17179108), +3142C/G (rs1063320), +3187A/G (rs9380142) and +3196C/G (rs1610696) in the exon 8 of the 3' untranslated regions (3' UTRs) using sanger sequencing method. Associations were assessed for five inheritance models (codominant, dominant, recessive, over-dominant and log-additive). Moreover, the levels of plasma soluble HLA-G (sHLA-G) were explored using ELISA method. Our results revealed that the 14-bp INS/DEL polymorphism was strongly associated with COVID-19 symptoms development for almost all tested inheritance models (p < 0.001). Inversely, the (+3196C/G) polymorphism exhibited a protective effect against COVID-19. In addition, three haplotypes; UTR-1, UTR-3, and UTR-5 were found associated with COVID-19 symptoms (p < 0.05), The level of HLA-G in the serum was significantly higher in COVID-19 individuals than in healthy individuals (p < 0.001).These findings suggest that HLA-G gene polymorphisms in the regulatory 3'UTR region of the HLA-G gene may influence the host immune response to SARS-CoV-2 infection. A deeper comprehension of the functional effect of these associated polymorphisms could be useful in identifying high-risk individuals and in developing adaptive treatments for patients.
本研究的目的是调查HLA - G基因变异和可溶性HLA - G（sHLA - G）与感染新型冠状病毒（SARS-CoV-2）易感性之间的关系。在这项病例对照研究中，对65例新冠肺炎患者和67名健康对照者进行基因分型，检测其主要功能多态性，即3'非翻译区（3'UTR）外显子8中的14bp插入/缺失（rs371194629）、+3003C/T（rs1707）、+3010C/G（rs1710）、+3027A/C（rs17179101）、+3035C/T（rs17179108）、+3142C/G（rs1063320）、+3187A/G（rs9380142）和+3196C/G（rs1610696），采用桑格测序法。评估了五种遗传模型（共显性、显性、隐性、超显性和对数加性）的关联性。此外，采用酶联免疫吸附测定（ELISA）法检测血浆可溶性HLA - G（sHLA - G）水平。我们的结果显示，对于几乎所有检测的遗传模型，14bp插入/缺失多态性与新冠肺炎症状发展密切相关（p＜0.001）。相反，（+3196C/G）多态性对新冠肺炎表现出保护作用。此外，发现三种单倍型UTR - 1、UTR - 3和UTR - 5与新冠肺炎症状相关（p＜0.05）。新冠肺炎患者血清中HLA - G水平显著高于健康个体（p＜0.001）。这些发现表明，HLA - G基因调控性3'UTR区域中的HLA - G基因多态性可能影响宿主对SARS-CoV-2感染的免疫反应。深入了解这些相关多态性的功能效应可能有助于识别高危个体并为患者制定适应性治疗方案。
