Association of genetic variations in ACE2, TIRAP and factor X with outcomes in COVID-19

Marissa J M Traets; Roel H T Nijhuis; Servaas A Morré; Sander Ouburg; Jasper A Remijn; Bastiaan A Blok; Bas de Laat; Eefje Jong; Gerarda J M Herder; Aernoud T L Fiolet; Stephan P Verweij

doi:10.1371/journal.pone.0260897

Association of genetic variations in ACE2, TIRAP and factor X with outcomes in COVID-19

Marissa J M Traets^*, Roel H T Nijhuis, Servaas A Morré, Sander Ouburg, Jasper A Remijn, Bastiaan A Blok, Bas de Laat, Eefje Jong, Gerarda J M Herder, Aernoud T L Fiolet, Stephan P Verweij

^*Corresponding author for this work

GROW - Reproductive and Perinatal Medicine

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with varying disease severity and mortality. Genetic predisposition influences the clinical course of infectious diseases. We investigated whether genetic polymorphisms in candidate genes ACE2, TIRAP, and factor X are associated with clinical outcomes in COVID-19.

METHODS: We conducted a single-centre retrospective cohort study. All patients who visited the emergency department with SARS-CoV-2 infection proven by polymerase chain reaction were included. Single nucleotide polymorphisms in ACE2 (rs2285666), TIRAP (rs8177374) and factor X (rs3211783) were assessed. The outcomes were mortality, respiratory failure and venous thromboembolism. Respiratory failure was defined as the necessity of >5 litres/minute oxygen, high flow nasal oxygen suppletion or mechanical ventilation.

RESULTS: Between March and April 2020, 116 patients (35% female, median age 65 [inter quartile range 55-75] years) were included and treated according to the then applicable guidelines. Sixteen patients (14%) died, 44 patients (38%) had respiratory failure of whom 23 required endotracheal intubation for mechanical ventilation, and 20 patients (17%) developed venous thromboembolism. The percentage of TIRAP polymorphism carriers in the survivor group was 28% as compared to 0% in the non-survivor group (p = 0.01, Bonferroni corrected p = 0.02). Genotype distribution of ACE2 and factor X did not differ between survivors and non-survivors.

CONCLUSION: This study shows that carriage of TIRAP polymorphism rs8177374 could be associated with a significantly lower mortality in COVID-19. This TIRAP polymorphism may be an important predictor in the outcome of COVID-19.

Original language	English
Article number	e0260897
Number of pages	12
Journal	PLOS ONE
Volume	17
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0260897
Publication status	Published - 7 Jan 2022

Keywords

Aged
Angiotensin-Converting Enzyme 2/genetics
COVID-19/epidemiology
Cohort Studies
Factor X/genetics
Female
Genetic Predisposition to Disease/genetics
Genotype
Humans
Male
Membrane Glycoproteins/genetics
Middle Aged
Netherlands/epidemiology
Polymorphism, Single Nucleotide/genetics
Receptors, Interleukin-1/genetics
Retrospective Studies
SARS-CoV-2/genetics
Severity of Illness Index
Treatment Outcome

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@article{f25c74d0884543fb8aa48543503027c6,

title = "Association of genetic variations in ACE2, TIRAP and factor X with outcomes in COVID-19",

abstract = "BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with varying disease severity and mortality. Genetic predisposition influences the clinical course of infectious diseases. We investigated whether genetic polymorphisms in candidate genes ACE2, TIRAP, and factor X are associated with clinical outcomes in COVID-19.METHODS: We conducted a single-centre retrospective cohort study. All patients who visited the emergency department with SARS-CoV-2 infection proven by polymerase chain reaction were included. Single nucleotide polymorphisms in ACE2 (rs2285666), TIRAP (rs8177374) and factor X (rs3211783) were assessed. The outcomes were mortality, respiratory failure and venous thromboembolism. Respiratory failure was defined as the necessity of >5 litres/minute oxygen, high flow nasal oxygen suppletion or mechanical ventilation.RESULTS: Between March and April 2020, 116 patients (35% female, median age 65 [inter quartile range 55-75] years) were included and treated according to the then applicable guidelines. Sixteen patients (14%) died, 44 patients (38%) had respiratory failure of whom 23 required endotracheal intubation for mechanical ventilation, and 20 patients (17%) developed venous thromboembolism. The percentage of TIRAP polymorphism carriers in the survivor group was 28% as compared to 0% in the non-survivor group (p = 0.01, Bonferroni corrected p = 0.02). Genotype distribution of ACE2 and factor X did not differ between survivors and non-survivors.CONCLUSION: This study shows that carriage of TIRAP polymorphism rs8177374 could be associated with a significantly lower mortality in COVID-19. This TIRAP polymorphism may be an important predictor in the outcome of COVID-19.",

keywords = "Aged, Angiotensin-Converting Enzyme 2/genetics, COVID-19/epidemiology, Cohort Studies, Factor X/genetics, Female, Genetic Predisposition to Disease/genetics, Genotype, Humans, Male, Membrane Glycoproteins/genetics, Middle Aged, Netherlands/epidemiology, Polymorphism, Single Nucleotide/genetics, Receptors, Interleukin-1/genetics, Retrospective Studies, SARS-CoV-2/genetics, Severity of Illness Index, Treatment Outcome",

author = "Traets, {Marissa J M} and Nijhuis, {Roel H T} and Morr{\'e}, {Servaas A} and Sander Ouburg and Remijn, {Jasper A} and Blok, {Bastiaan A} and {de Laat}, Bas and Eefje Jong and Herder, {Gerarda J M} and Fiolet, {Aernoud T L} and Verweij, {Stephan P}",

note = "Publisher Copyright: {\textcopyright} 2022 Traets et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2022",

month = jan,

day = "7",

doi = "10.1371/journal.pone.0260897",

language = "English",

volume = "17",

journal = "PLOS ONE",

issn = "1932-6203",

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T1 - Association of genetic variations in ACE2, TIRAP and factor X with outcomes in COVID-19

AU - Traets, Marissa J M

AU - Nijhuis, Roel H T

AU - Morré, Servaas A

AU - Ouburg, Sander

AU - Remijn, Jasper A

AU - Blok, Bastiaan A

AU - de Laat, Bas

AU - Jong, Eefje

AU - Herder, Gerarda J M

AU - Fiolet, Aernoud T L

AU - Verweij, Stephan P

N1 - Publisher Copyright: © 2022 Traets et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2022/1/7

Y1 - 2022/1/7

N2 - BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with varying disease severity and mortality. Genetic predisposition influences the clinical course of infectious diseases. We investigated whether genetic polymorphisms in candidate genes ACE2, TIRAP, and factor X are associated with clinical outcomes in COVID-19.METHODS: We conducted a single-centre retrospective cohort study. All patients who visited the emergency department with SARS-CoV-2 infection proven by polymerase chain reaction were included. Single nucleotide polymorphisms in ACE2 (rs2285666), TIRAP (rs8177374) and factor X (rs3211783) were assessed. The outcomes were mortality, respiratory failure and venous thromboembolism. Respiratory failure was defined as the necessity of >5 litres/minute oxygen, high flow nasal oxygen suppletion or mechanical ventilation.RESULTS: Between March and April 2020, 116 patients (35% female, median age 65 [inter quartile range 55-75] years) were included and treated according to the then applicable guidelines. Sixteen patients (14%) died, 44 patients (38%) had respiratory failure of whom 23 required endotracheal intubation for mechanical ventilation, and 20 patients (17%) developed venous thromboembolism. The percentage of TIRAP polymorphism carriers in the survivor group was 28% as compared to 0% in the non-survivor group (p = 0.01, Bonferroni corrected p = 0.02). Genotype distribution of ACE2 and factor X did not differ between survivors and non-survivors.CONCLUSION: This study shows that carriage of TIRAP polymorphism rs8177374 could be associated with a significantly lower mortality in COVID-19. This TIRAP polymorphism may be an important predictor in the outcome of COVID-19.

AB - BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can manifest with varying disease severity and mortality. Genetic predisposition influences the clinical course of infectious diseases. We investigated whether genetic polymorphisms in candidate genes ACE2, TIRAP, and factor X are associated with clinical outcomes in COVID-19.METHODS: We conducted a single-centre retrospective cohort study. All patients who visited the emergency department with SARS-CoV-2 infection proven by polymerase chain reaction were included. Single nucleotide polymorphisms in ACE2 (rs2285666), TIRAP (rs8177374) and factor X (rs3211783) were assessed. The outcomes were mortality, respiratory failure and venous thromboembolism. Respiratory failure was defined as the necessity of >5 litres/minute oxygen, high flow nasal oxygen suppletion or mechanical ventilation.RESULTS: Between March and April 2020, 116 patients (35% female, median age 65 [inter quartile range 55-75] years) were included and treated according to the then applicable guidelines. Sixteen patients (14%) died, 44 patients (38%) had respiratory failure of whom 23 required endotracheal intubation for mechanical ventilation, and 20 patients (17%) developed venous thromboembolism. The percentage of TIRAP polymorphism carriers in the survivor group was 28% as compared to 0% in the non-survivor group (p = 0.01, Bonferroni corrected p = 0.02). Genotype distribution of ACE2 and factor X did not differ between survivors and non-survivors.CONCLUSION: This study shows that carriage of TIRAP polymorphism rs8177374 could be associated with a significantly lower mortality in COVID-19. This TIRAP polymorphism may be an important predictor in the outcome of COVID-19.

KW - Aged

KW - Angiotensin-Converting Enzyme 2/genetics

KW - COVID-19/epidemiology

KW - Cohort Studies

KW - Factor X/genetics

KW - Female

KW - Genetic Predisposition to Disease/genetics

KW - Genotype

KW - Humans

KW - Male

KW - Membrane Glycoproteins/genetics

KW - Middle Aged

KW - Netherlands/epidemiology

KW - Polymorphism, Single Nucleotide/genetics

KW - Receptors, Interleukin-1/genetics

KW - Retrospective Studies

KW - SARS-CoV-2/genetics

KW - Severity of Illness Index

KW - Treatment Outcome

U2 - 10.1371/journal.pone.0260897

DO - 10.1371/journal.pone.0260897

M3 - Article

C2 - 34995294

SN - 1932-6203

VL - 17

JO - PLOS ONE

JF - PLOS ONE

IS - 1

M1 - e0260897

ER -

Association of genetic variations in ACE2, TIRAP and factor X with outcomes in COVID-19

Abstract

Keywords

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