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Association between HLA gene polymorphisms and mortality of COVID-19: An in silico analysis.

ABSTRACT: INTRODUCTION:The emergence of SARS-CoV-2 has caused global public health and economic crisis. Human leukocyte antigen (HLA) is a critical component of the viral antigen presentation pathway and plays essential roles in conferring differential viral susceptibility and severity of diseases. However, the association between HLA gene polymorphisms and risk for COVID-19 has not been fully elucidated. We hypothesized that HLA genotypes might impact on the differences in morbidity and mortality of COVID-19 across countries. METHODS:We conducted in silico analyses and examined an association of HLA gene polymorphisms with prevalence and mortality of COVID-19 by using publicly available databases. RESULTS:We found that a possible association between HLA-A*02:01 and an increased risk for COVID-19. HLA-A*02:01 had a relatively lower capacity to present SARS-CoV-2 antigens compared with other frequent HLA class I molecules, HLA-A*11:01 or HLA-A*24:02. CONCLUSION:This study suggests that individuals with HLA-A*11:01 or HLA-A*24:02 genotypes may generate efficiently T-cell-mediated antiviral responses to SARS-CoV-2 compared with HLA-A*02:01. The differences in HLA genotypes may potentially alter the course of the disease and its transmission.

SUBMITTER: Tomita Y

PROVIDER: S-EPMC7654404 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Association between HLA gene polymorphisms and mortality of COVID-19: An in silico analysis.

Tomita Yusuke Y Ikeda Tokunori T Sato Ryo R Sakagami Takuro T

Immunity, inflammation and disease 20201013 4

<h4>Introduction</h4>The emergence of SARS-CoV-2 has caused global public health and economic crisis. Human leukocyte antigen (HLA) is a critical component of the viral antigen presentation pathway and plays essential roles in conferring differential viral susceptibility and severity of diseases. However, the association between HLA gene polymorphisms and risk for COVID-19 has not been fully elucidated. We hypothesized that HLA genotypes might impact on the differences in morbidity and mortality ...[more]

PMID: 33047883

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Project description:Coronavirus disease 2019 (COVID-19) is a severe disease caused by a new variant of beta-coronavirus that first appeared in China. Human genetic factors, including polymorphisms, serve pivotal roles in the high transmission of SARS-CoV-2 and the stubbornly progressing sickness seen in a small but significant percentage of infected people; however, but these factors remain ill-defined. A total of 288 COVID-19 patients and 288 controls were genotyped for TMPRSS2 polymorphisms using both restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and amplification refractory mutation system (ARMS)-PCR techniques. Different genotypes of TMPRSS2 polymorphisms were compared in terms of disease susceptibility and mortality. The statistical analysis showed that minor alleles of all studied variants statistically increased the risk of COVID-19, except for the rs75603675 C > A variant. The T allele of rs12329760 conferred an increased risk of COVID-19. Moreover, the AG/AC/TT/AG combination of genotypes significantly enhanced the risk of COVID-19 in our population. Different haplotypes of rs17854725/rs75603675/rs12329760/rs4303795 polymorphisms, including GACA, GACG, GATG, GATA, AATA, ACCG, ACTG, ACTA, GCCA, and GCTG, were found to be associated with increased risk of the disease (odds ratio > 1). Regarding the clinical and paraclinical characteristics, a statistically significant difference was found between non-severe and severe forms except for gender, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and underlying diseases. In addition, case genotypes of TMPRSS2 rs17854725 A > G, rs12329760 C > T, and rs4303795 A > G were significantly different regarding severe and non-severe forms of the disease (P-value < 0.001). Specifically, death was more frequent in carriers of the AG genotype of rs17854725 A > G (P-value = 0.022). Patients who carry the minor alleles of the four studied TMPRSS2 variants were rather vulnerable to COVID-19 infection. Our findings indicated that rs17854725 A > G (AA vs. AG and AA vs. GG), rs12329760 C > T (CC vs. CT and CC vs. TT), and rs4303795 A > G (AA vs. AG) genotypes of TMPRSS2 variations are associated with a more invasive disorder pattern. More studies on larger populations are needed to confirm our results.

Dataset Information

Association between HLA gene polymorphisms and mortality of COVID-19: An in silico analysis.

Publications

Association between HLA gene polymorphisms and mortality of COVID-19: An in silico analysis.

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