Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients

Wulandari, Laksmi; Hamidah, Berliana; Pakpahan, Cennikon; Damayanti, Nevy Shinta; Kurniati, Neneng Dewi; Adiatmaja, Christophorus Oetama; Wigianita, Monica Rizky; Soedarsono, -; Husada, Dominicus; Tinduh, Damayanti; Prakoeswa, Cita Rosita Sigit; Endaryanto, Anang; Puspaningsih, Ni Nyoman Tri; Mori, Yasuko; Lusida, Maria Inge; Shimizu, Kazufumi; Oceandy, Delvac

doi:10.1186/s40246-021-00330-7

Cited by 45 publications

(47 citation statements)

References 32 publications

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“…For the association study, we searched for the studies on TMPRSS2 gene variants reported in the literature elsewhere in relation to COVID-19 susceptibility ( Mollica et al, 2020 ; Andolfo et al, 2021 ; Asselta et al, 2020 ; Bhattacharyya et al, 2020 ; Darbani, 2020 ; Hou et al, 2020 ; Irham et al, 2020 ; Iyer et al, 2020 ; Jeon et al, 2020 ; Kim and Jeong, 2021 ; Latini et al, 2020 ; Paniri et al, 2021 ; Piva et al, 2021 ; Ragia and Manolopoulos, 2020 ; Senapati et al, 2020 ; Sharma et al, n.d. ; Singh et al, 2021 ; Strope et al, 2020 ; Torre-Fuentes et al, 2021 ; Vargas-Alarcón et al, 2020 ; Wang et al, 2020 ; Wulandari et al, 2021 ; Saih et al, 2021 ; Schönfelder et al, 2021 ; Kehdy et al, 2021 ) from this a total of 5 SNPs (rs2070788, rs734056, rs12329760, rs2276205, and rs3787950) was observed in our data and studied subsequently in detail. Data from the Estonian Biocentre ( Chaubey et al, 2017 ; Pathak et al, 2018 ; Re3data, 2014 ; Tätte et al, 2019 ), phase 3 of the 1000 Genomes Project ( Durbin et al, 2010 ), and our new genotyped samples from several Indian states were used to calculate the frequency of each of these SNPs among various Indian populations using plink 1.9.…”

Section: Methodssupporting

confidence: 59%

Genetic association of TMPRSS2 rs2070788 polymorphism with COVID-19 case fatality rate among Indian populations

Pandey

Srivastava

Singh

et al. 2022

Infection, Genetics and Evolution

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SARS-CoV-2, the causative agent for COVID-19, an ongoing pandemic, engages the ACE2 receptor to enter the host cell through S protein priming by a serine protease, TMPRSS2 . Variation in the TMPRSS2 gene may account for the disparity in disease susceptibility between populations. Therefore, in the present study, we have used next-generation sequencing (NGS) data of world populations from 393 individuals and analyzed the TMPRSS2 gene using a haplotype-based approach with a major focus on South Asia to study its phylogenetic structure and their haplotype sharing among various populations worldwide. Our analysis of phylogenetic relatedness showed a closer affinity of South Asians with the West Eurasian populations therefore, host disease susceptibility and severity particularly in the context of TMPRSS2 will be more akin to West Eurasian instead of East Eurasian. This is in contrast to our prior study on the ACE2 gene which shows South Asian haplotypes have a strong affinity towards West Eurasians. Thus ACE2 and TMPRSS2 have an antagonistic genetic relatedness among South Asians. Considering the significance of the TMPRSS2 gene in the SARS-CoV-2 pathogenicity, COVID-19 infection and intensity trends could be directly associated with increased expression therefore, we have also tested the SNPs frequencies of this gene among various Indian state populations with respect to the case fatality rate (CFR). Interestingly, we found a significant positive association between the rs2070788 SNP (G Allele) and the CFR among Indian populations. Further our cis eQTL analysis of rs2070788 shows that the GG genotype of the rs2070788 tends to have a significantly higher expression of TMPRSS2 gene in the lung compared to the AG and AA genotypes thus validating the previous observation and therefore it might play a vital part in determining differential disease vulnerability. We trust that this information will be useful in understanding the role of the TMPRSS2 variant in COVID-19 susceptibility and using it as a biomarker may help to predict populations at risk.

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Section: Methodssupporting

confidence: 59%

Genetic association of TMPRSS2 rs2070788 polymorphism with COVID-19 case fatality rate among Indian populations

Pandey

Srivastava

Singh

et al. 2022

Infection, Genetics and Evolution

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“…TMPRSS2 act as co-receptor for SARS-CoV-2 cell invasion and it's high expression will lead to increased susceptibility for COVID-19. 32,33 The mean age of all the subjects in our study was 59 years old, with the youngest subject over 50 years old. Older people were more sensitive to SARS-CoV-2 infection and had a higher positive rate than younger age.…”

Section: Discussionmentioning

confidence: 91%

Inflammatory laboratory findings associated with severe illness among hospitalized individuals with COVID-19 in Medan, Indonesia: a cross-sectional study

et al. 2021

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Background: Coronavirus disease (COVID-19) is still a global health problem. COVID-19 patients with severe pneumonia have a higher risk for critical illness, mostly complicated by acute respiratory distress syndrome. The inflammatory response is critical, and the cytokine storm increases severity of COVID-19. Many factors could be associated with a cytokine storm but these are incompletely understood. The aim of this study is to present characteristics of patients with COVID-19 and explore the clinical and inflammatory parameters of severe and critically ill COVID-19 patients in the intensive care unit (ICU). Method: The cross-sectional study was conducted in all severe COVID-19 patients admitted to the ICU. Peripheral blood was taken for laboratory examination within 24 hours of admission. Hematologic parameters, serum electrolyte, renal function, liver function, pancreas enzyme, D-dimer, inflammatory cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, monocyte chemoattractant protein-1 (MCP-1), and C-reactive protein (CRP) were assessed in this study. Comparison analyses were done between sex, comorbidity existed, body mass index (BMI), and vaccination status. Results: A total of 80 subjects were included in the study. The most frequent comorbidities found among the subjects were obesity (36.35%) and diabetes (22.5%). Only 13.75% of subjects were vaccinated. Laboratory results indicated leukocytosis and neutrophilia, with neutrophil-lymphocyte-ratio (NLR) of 7. The mean inflammatory findings (IL-6, IL-10, TNF-alpha, IFN-gamma, MCP-1), D-dimer, CRP, and lipase increased. Lipase levels were higher in men (p=0.003) and in comorbidity groups. No significant differences found with different BMI groups. Lipase, IL-6, and MCP-1 levels were significantly higher (p=0.019, <0.0001, and 0.03, respectively) in the non-vaccinated group. Conclusions: Most patients with severe COVID-19 have comorbidities and increased inflammatory markers.

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“…TMPRSS2 acts as a co-receptor for SARS-CoV-2 cell invasion, and its high expression will lead to increased susceptibility for COVID-19. 32 , 33 …”

Section: Discussionmentioning

confidence: 99%

Inflammatory laboratory findings associated with severe illness among hospitalized individuals with COVID-19 in Medan, Indonesia: a cross-sectional study

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background: Coronavirus disease (COVID-19) remains a global health problem. COVID-19 patients with severe pneumonia have a higher risk for critical illness, mostly complicated by acute respiratory distress syndrome. The inflammatory response is critical, and the cytokine storm increases the severity of COVID-19. Many factors could be associated with a cytokine storm but they are incompletely understood. This study presents characteristics of COVID-19 patients and explore the clinical and inflammatory parameters of severe and critically ill COVID-19 patients in the intensive care unit (ICU). Method: This cross-sectional study was conducted in all severe COVID-19 patients admitted to the ICU. Peripheral blood was taken for laboratory examination within 24 hours of admission. Haematologic parameters, serum electrolyte, renal function, liver function, pancreas enzyme, D-dimer, inflammatory cytokines interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, monocyte chemoattractant protein-1 (MCP-1), and C-reactive protein (CRP) were assessed in this study. Comparative analyses were done between sex, existing comorbidities, body mass index (BMI), and COVID-19 vaccination status. Results: A total of 80 subjects were included in the study. The most frequent comorbidities found among the subjects were obesity (36.35%) and diabetes (22.5%). Only 13.75% of subjects were vaccinated. Laboratory results indicated leucocytosis and neutrophilia, with a neutrophil-lymphocyte-ratio (NLR) of 7. The mean inflammatory findings (IL-6, IL-10, TNF-alpha, IFN-gamma, MCP-1), D-dimer, CRP, and lipase increased. Lipase levels were higher in men (p = 0.003) and in comorbidity groups. No significant differences were found among different BMI groups. Lipase, IL-6, and MCP-1 levels were significantly higher (p=0.019, <0.0001, and 0.03, respectively) in the non-vaccinated group. Conclusions: Most patients with severe COVID-19 have comorbidities and increased inflammatory markers.

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Initial study on TMPRSS2 p.Val160Met genetic variant in COVID-19 patients

Cited by 45 publications

References 32 publications

Genetic association of TMPRSS2 rs2070788 polymorphism with COVID-19 case fatality rate among Indian populations

Genetic association of TMPRSS2 rs2070788 polymorphism with COVID-19 case fatality rate among Indian populations

Inflammatory laboratory findings associated with severe illness among hospitalized individuals with COVID-19 in Medan, Indonesia: a cross-sectional study

Inflammatory laboratory findings associated with severe illness among hospitalized individuals with COVID-19 in Medan, Indonesia: a cross-sectional study

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