| Summary: | Since the emergence and rapid transmission of SARS-CoV-2, numerous scientific reports have searched for the association of host genetic variants with COVID-19, but the data are mostly acquired from Europe. In the current work, we explored the link between host genes (SARS-CoV-2 entry and immune system related to COVID-19 sensitivity/severity) and ABO blood types with COVID-19 from whole-exome data of 200 COVID-19 patients and 100 controls in Vietnam. The O blood type was found to be a protective factor that weakens the worst outcomes of infected individuals. For SARS-CoV-2 susceptibility, rs2229207 (TC genotype, allele C) and rs17860118 (allele T) of <i>IFNAR2</i> increased the risk of infection, but rs139940581 (CT genotype, allele T) of <i>SLC6A20</i> reduced virus sensitivity. For COVID-19 progress, the frequencies of rs4622692 (TG genotype) and rs1048610 (TC genotype) of <i>ADAM17</i> were significantly higher in the moderate group than in the severe/fatal group. The variant rs12329760 (AA genotype) of <i>TMPRSS2</i> was significantly associated with asymptomatic/mild symptoms. Additionally, rs2304255 (CT genotype, allele T) of <i>TYK2</i> and rs2277735 (AG genotype) of <i>DPP9</i> were associated with severe/fatal outcomes. Studies on different populations will give better insights into the pathogenesis, which is ethnic-dependent, and thus decipher the genetic factor’s contribution to mechanisms that predispose people to being more vulnerable to COVID-19.
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