Relationships between Polymorphisms in HLA-G 3’UTR Region and COVID- 19 Disease Severity

Abstract

This study aims to discover how HLA-G gene variations and sHLA-G, as well as other host genetic factors, can affect SARS-CoV-2 infection. In this case-control study, 67 Patients with COVID-19 were and 65 healthy controls were genotyped for their main functional polymorphisms in the exon 8 of the 3' untranslated regions (3' UTRs) using sanger sequencing. Associations were assessed for five inheritance models (co-dominant, 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 all-main polymorphism in the 3’UTR region previously described for the HLA-G 3’UTR, 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). 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. 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 host genetics could be useful in identifying high-risk individuals and in the development of better treatments or vaccinations.