Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Medical University, 1 Ostrovityanova Street, 117997 Moscow, Russia.
Int J Mol Sci. 2023 Feb 4;24(4):3068. doi: 10.3390/ijms24043068.
HLA genes play a pivotal role in the immune response via presenting the pathogen peptides on the cell surface in a host organism. Here, we studied the association of HLA allele variants of class I (loci A, B, C) and class II (loci DRB1, DQB1, DPB1) genes with the outcome of COVID-19 infection. We performed high-resolution sequencing of class HLA I and class II genes based on the sample population of 157 patients who died from COVID-19 and 76 patients who survived despite severe symptoms. The results were further compared with HLA genotype frequencies in the control population represented by 475 people from the Russian population. Although the obtained data revealed no significant differences between the samples at a locus level, they allowed one to uncover a set of notable alleles potentially contributing to the COVID-19 outcome. Our results did not only confirm the previously discovered fatal role of age or association of DRB101:01:01G and DRB101:02:01G alleles with severe symptoms and survival, but also allowed us to single out the DQB105:03:01G allele and B14:02:01G~C*08:02:01G haplotype, which were associated with survival. Our findings showed that not only separate allele, but also their haplotype, could serve as potential markers of COVID-19 outcome and be used during triage for hospital admission.
HLA 基因通过在宿主生物体的细胞表面呈现病原体肽,在免疫反应中发挥关键作用。在这里,我们研究了 HLA Ⅰ类(A、B、C 座)和Ⅱ类(DRB1、DQB1、DPB1 座)基因的等位基因变异与 COVID-19 感染结果的关联。我们对来自 157 名死于 COVID-19 的患者和 76 名尽管有严重症状但幸存的患者的样本进行了 HLA I 类和 II 类基因的高分辨率测序。将结果与由来自俄罗斯人群的 475 人代表的对照人群中的 HLA 基因型频率进行了进一步比较。尽管在基因座水平上获得的数据未显示样本之间存在显著差异,但它们允许发现一组可能有助于 COVID-19 结果的显著等位基因。我们的结果不仅证实了先前发现的年龄或 DRB101:01:01G 和 DRB101:02:01G 等位基因与严重症状和存活相关的致命作用,而且还允许我们单独鉴定出与存活相关的 DQB105:03:01G 等位基因和 B14:02:01G~C*08:02:01G 单倍型。我们的研究结果表明,不仅是单独的等位基因,还有它们的单倍型,都可以作为 COVID-19 结果的潜在标志物,并在住院时进行分诊中使用。