TMPRSS2 polymorphism (rs12329760) and the severity of the COVID-19 in Iranian population

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the recent pandemic since early 2020. Due to the wide range of clinical symptoms of this disease, from asymptomatic to severe and critical forms, it seems that genetic differences among patients, along with other factors (such as gender, age, and underlying diseases), can explain part of the variation in disease symptoms. The TMPRSS2 enzyme plays a vital role in the early stages of the interaction of the SARS-CoV-2 with the host cells by facilitating viral entry. There is a polymorphism in the TMPRSS2 gene, called rs12329760(C to T) as a missense variant, which causes the replacement of valine to methionine in the TMPRSS2 protein at position 160. The present study investigated the association between the TMPRSS2 genotype and the severity of the Coronavirus disease 2019 (COVID-19) in Iranian patients. The TMPRSS2 genotype of 251 COVID-19 patients (151 patients with asymptomatic to mild and 100 patients with severe to critical symptoms) was detected on genomic DNA extracted from patients’ peripheral blood via the ARMS-PCR method. Our results showed a significant association between the minor T allele and the severity of the COVID-19 (P-value = 0.043) under the dominant and additive inheritance model. In conclusion, the results of this study showed that the T allele of the rs12329760 in the TMPRSS2 gene is a risk allele for severe form of COVID-19 in Iranian patients in contrast to most previous studies on this variant in European ancestry populations which suggested this variant as a protective allele. Our results reiterate to the ethnic-specific risk alleles and hidden unknown complexity behind the host genetic susceptibility. However, further studies are needed to address the complex mechanisms behind the interaction of the TMPRSS2 protein and the SARS-CoV-2 and the role of rs12329760 polymorphism in determining the disease severity.

Genetic variants in ATP2B2 as risk factors for mortality in patients unrelated but not associated with families with severe COVID-19

“…The rs12329769 in TMPRSS2 in a recessive genetic model (CC + CT vs. TT) has been associated with severe COVID-19 and high levels of inflammatory markers such as C-reactive protein (CRP), ferritin, LDH, and D-Dimer [ 23 ]. The role of TMPRSS2 in cell entry of SARS-CoV-2 could explain the association with COVID-19 susceptibility found in some studies [ 38 ]. The missense variant rs12329769 (Val197Met) is in the coding part of the gene.…”

Evaluation of relationship between TMPRSS2 p.(Val197Met) variant and COVID-19 susceptibility and severity

“…Among the 21 single nucleotide variants (SNVs) in the TMPRSS2 gene, a computational study has revealed that the p.Val197Met variant affects this enzyme's structure by creating a pocket in the protein structure. This can lower enzyme activity and stability, which is anticipated to protect against SARS-CoV-2 infection by reducing SARS-CoV-2 activation and entrance into host cells [ 6 – 8 ].…”

“…However, none of those differences were statistically significant, with a p -value of 0.074. Additionally, the study discovered a statistically significant link between COVID-19 severity and the minor T allele [ 8 ].…”

“…The connection of the TMPRSS2 gene variation with COVID-19 severity was investigated in several pieces of research, although the findings needed to be more consistent. More research is necessary to fully comprehend the intricate mechanisms underlying the relationship between TMPRSS2 and SARS-CoV-2 and the significance of the p.Val197Met variant in determining disease severity [ 8 ].…”

Host Genetics and COVID-19: Genes Underlying the Patterns of Susceptibility and Prognosis

“…39 The rs12329760 has been suggested as one of the candidate polymorphisms to justify the high incidence and SARS-CoV-2 infection-related mortality rate in Italians, when compared to other European populations. 40 Yaghoobi et al 41 reported that in Iranian patients, the T allele of rs12329760 can be considered a risk allele for severe COVID-19. In contrast, previous studies on this variant in European populations have suggested that the T allele has a protective effect.…”