Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study

(1) Background: Sepsis is a leading cause of death and a global public health problem. Accordingly, deciphering the underlying molecular mechanisms of this disease and the determinants of its morbidity and mortality is pivotal. This study examined the effect of the rs951818 SNP of the negative costi...

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Autores principales:	Caspar Mewes, Tessa Alexander, Benedikt Büttner, José Hinz, Ayelet Alpert, Aron-F. Popov, Tim Beißbarth, Mladen Tzvetkov, Marian Grade, Michael Quintel, Ingo Bergmann, Ashham Mansur
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	LAG-3 lymphocyte-activation gene 3 single nucleotide polymorphism genetic association study sepsis mortality Medicine R
Acceso en línea:	https://doaj.org/article/36888c994df64f12935d94fabe780b64
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spelling	oai:doaj.org-article:36888c994df64f12935d94fabe780b642021-11-25T18:01:34ZEffect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study10.3390/jcm102253022077-0383https://doaj.org/article/36888c994df64f12935d94fabe780b642021-11-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/22/5302https://doaj.org/toc/2077-0383(1) Background: Sepsis is a leading cause of death and a global public health problem. Accordingly, deciphering the underlying molecular mechanisms of this disease and the determinants of its morbidity and mortality is pivotal. This study examined the effect of the rs951818 SNP of the negative costimulatory lymphocyte-activation gene 3 (LAG-3) on sepsis mortality and disease severity. (2) Methods: 707 consecutive patients with sepsis were prospectively enrolled into the present study from three surgical ICUs at University Medical Center Goettingen. Both 28- and 90-day mortality were analyzed as the primary outcome, while parameters of disease severity served as secondary endpoints. (3) Results: In the Kaplan–Meier analysis LAG-3 rs951818 AA-homozygote patients showed a significantly lower 28-day mortality (17.3%) compared to carriers of the C-allele (23.7%, <i>p</i> = 0.0476). In addition, these patients more often received invasive mechanical ventilation (96%) during the course of disease than C-allele carriers (92%, <i>p</i> = 0.0466). (4) Conclusions: Genetic profiling of LAG-3 genetic variants alone or in combination with other genetic biomarkers may represent a promising approach for risk stratification of patients with sepsis. Patient-individual therapeutic targeting of immune checkpoints, such as LAG-3, may be a future component of sepsis therapy. Further detailed investigations in clinically relevant sepsis models are necessary.Caspar MewesTessa AlexanderBenedikt BüttnerJosé HinzAyelet AlpertAron-F. PopovTim BeißbarthMladen TzvetkovMarian GradeMichael QuintelIngo BergmannAshham MansurMDPI AGarticleLAG-3lymphocyte-activation gene 3single nucleotide polymorphismgenetic association studysepsismortalityMedicineRENJournal of Clinical Medicine, Vol 10, Iss 5302, p 5302 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	LAG-3 lymphocyte-activation gene 3 single nucleotide polymorphism genetic association study sepsis mortality Medicine R
spellingShingle	LAG-3 lymphocyte-activation gene 3 single nucleotide polymorphism genetic association study sepsis mortality Medicine R Caspar Mewes Tessa Alexander Benedikt Büttner José Hinz Ayelet Alpert Aron-F. Popov Tim Beißbarth Mladen Tzvetkov Marian Grade Michael Quintel Ingo Bergmann Ashham Mansur Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
description	(1) Background: Sepsis is a leading cause of death and a global public health problem. Accordingly, deciphering the underlying molecular mechanisms of this disease and the determinants of its morbidity and mortality is pivotal. This study examined the effect of the rs951818 SNP of the negative costimulatory lymphocyte-activation gene 3 (LAG-3) on sepsis mortality and disease severity. (2) Methods: 707 consecutive patients with sepsis were prospectively enrolled into the present study from three surgical ICUs at University Medical Center Goettingen. Both 28- and 90-day mortality were analyzed as the primary outcome, while parameters of disease severity served as secondary endpoints. (3) Results: In the Kaplan–Meier analysis LAG-3 rs951818 AA-homozygote patients showed a significantly lower 28-day mortality (17.3%) compared to carriers of the C-allele (23.7%, <i>p</i> = 0.0476). In addition, these patients more often received invasive mechanical ventilation (96%) during the course of disease than C-allele carriers (92%, <i>p</i> = 0.0466). (4) Conclusions: Genetic profiling of LAG-3 genetic variants alone or in combination with other genetic biomarkers may represent a promising approach for risk stratification of patients with sepsis. Patient-individual therapeutic targeting of immune checkpoints, such as LAG-3, may be a future component of sepsis therapy. Further detailed investigations in clinically relevant sepsis models are necessary.
format	article
author	Caspar Mewes Tessa Alexander Benedikt Büttner José Hinz Ayelet Alpert Aron-F. Popov Tim Beißbarth Mladen Tzvetkov Marian Grade Michael Quintel Ingo Bergmann Ashham Mansur
author_facet	Caspar Mewes Tessa Alexander Benedikt Büttner José Hinz Ayelet Alpert Aron-F. Popov Tim Beißbarth Mladen Tzvetkov Marian Grade Michael Quintel Ingo Bergmann Ashham Mansur
author_sort	Caspar Mewes
title	Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title_short	Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title_full	Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title_fullStr	Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title_full_unstemmed	Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study
title_sort	effect of the lymphocyte activation gene 3 polymorphism rs951818 on mortality and disease progression in patients with sepsis—a prospective genetic association study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/36888c994df64f12935d94fabe780b64
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Effect of the Lymphocyte Activation Gene 3 Polymorphism rs951818 on Mortality and Disease Progression in Patients with Sepsis—A Prospective Genetic Association Study

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