Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients

Prostaglandin E2 (PGE2) is a major actor mediating renal injury. We aimed to determine genetic variability in the genes coding for its receptors (PTGER1-4) and study associations with nephrosclerosis risk and clinical outcomes. We identified 96 tag-SNPs capturing global variability in PTGER1-4 and s...

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Autores: González, Luz María, Robles, Nicolás Roberto, Mota Zamorano, Sonia, Valdivielso Revilla, José Manuel, López Gómez, Juan, Gervasini, Guillermo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/73322
Acceso en línea:https://doi.org/10.3390/jpm11080772
http://hdl.handle.net/10459.1/73322
Access Level:acceso abierto
Palabra clave:EP receptors
PGE2
Cardiovascular risk
Nephrosclerosis
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spelling Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These PatientsGonzález, Luz MaríaRobles, Nicolás RobertoMota Zamorano, SoniaValdivielso Revilla, José ManuelLópez Gómez, JuanGervasini, GuillermoEP receptorsPGE2Cardiovascular riskNephrosclerosisProstaglandin E2 (PGE2) is a major actor mediating renal injury. We aimed to determine genetic variability in the genes coding for its receptors (PTGER1-4) and study associations with nephrosclerosis risk and clinical outcomes. We identified 96 tag-SNPs capturing global variability in PTGER1-4 and screened 1209 nephrosclerosis patients and controls. The effect of these variants was evaluated by multivariate regression analyses. Two PTGER3 SNPs, rs11209730 and rs10399704, remained significant in a backward elimination regression model with other non-genetic variables (OR = 1.45 (1.07-1.95), p = 0.016 and OR = 0.71 (0.51-0.99), p = 0.041, respectively). In the nephrosclerosis patients, a proximal region of PTGER3 was tagged as relevant for eGFR (p values for identified SNPs ranged from 0.0003 to 0.038). Two consecutive PTGER3 SNPs, rs2284362 and rs2284363, significantly decreased systolic (p = 0.005 and p = 0.0005), diastolic (p = 0.039 and p = 0.005), and pulse pressure values (p = 0.038 and 0.014). Patients were followed for a median of 47 months (7-54) to evaluate cardiovascular (CV) risk. Cox regression analysis showed that carriers of the PTGER1rs2241360 T variant had better CV event-free survival than wild-type individuals (p = 0.029). In addition, PTGER3rs7533733 GG carriers had lower event-free survival than AA/AG patients (p = 0.011). Our results indicate that genetic variability in PGE2 receptors, particularly EP3, may be clinically relevant for nephrosclerosis and its associated CV risk.MDPI2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.3390/jpm11080772http://hdl.handle.net/10459.1/73322reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.3390/jpm11080772Journal of Personalized Medicine, 2021, vol. 18, núm. 8cc-by (c)Authors, 2021info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:recercat.cat:10459.1/733222026-05-29T05:05:01Z
dc.title.none.fl_str_mv Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients
title Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients
spellingShingle Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients
González, Luz María
EP receptors
PGE2
Cardiovascular risk
Nephrosclerosis
title_short Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients
title_full Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients
title_fullStr Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients
title_full_unstemmed Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients
title_sort Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients
dc.creator.none.fl_str_mv González, Luz María
Robles, Nicolás Roberto
Mota Zamorano, Sonia
Valdivielso Revilla, José Manuel
López Gómez, Juan
Gervasini, Guillermo
author González, Luz María
author_facet González, Luz María
Robles, Nicolás Roberto
Mota Zamorano, Sonia
Valdivielso Revilla, José Manuel
López Gómez, Juan
Gervasini, Guillermo
author_role author
author2 Robles, Nicolás Roberto
Mota Zamorano, Sonia
Valdivielso Revilla, José Manuel
López Gómez, Juan
Gervasini, Guillermo
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv EP receptors
PGE2
Cardiovascular risk
Nephrosclerosis
topic EP receptors
PGE2
Cardiovascular risk
Nephrosclerosis
description Prostaglandin E2 (PGE2) is a major actor mediating renal injury. We aimed to determine genetic variability in the genes coding for its receptors (PTGER1-4) and study associations with nephrosclerosis risk and clinical outcomes. We identified 96 tag-SNPs capturing global variability in PTGER1-4 and screened 1209 nephrosclerosis patients and controls. The effect of these variants was evaluated by multivariate regression analyses. Two PTGER3 SNPs, rs11209730 and rs10399704, remained significant in a backward elimination regression model with other non-genetic variables (OR = 1.45 (1.07-1.95), p = 0.016 and OR = 0.71 (0.51-0.99), p = 0.041, respectively). In the nephrosclerosis patients, a proximal region of PTGER3 was tagged as relevant for eGFR (p values for identified SNPs ranged from 0.0003 to 0.038). Two consecutive PTGER3 SNPs, rs2284362 and rs2284363, significantly decreased systolic (p = 0.005 and p = 0.0005), diastolic (p = 0.039 and p = 0.005), and pulse pressure values (p = 0.038 and 0.014). Patients were followed for a median of 47 months (7-54) to evaluate cardiovascular (CV) risk. Cox regression analysis showed that carriers of the PTGER1rs2241360 T variant had better CV event-free survival than wild-type individuals (p = 0.029). In addition, PTGER3rs7533733 GG carriers had lower event-free survival than AA/AG patients (p = 0.011). Our results indicate that genetic variability in PGE2 receptors, particularly EP3, may be clinically relevant for nephrosclerosis and its associated CV risk.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.3390/jpm11080772
http://hdl.handle.net/10459.1/73322
url https://doi.org/10.3390/jpm11080772
http://hdl.handle.net/10459.1/73322
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/jpm11080772
Journal of Personalized Medicine, 2021, vol. 18, núm. 8
dc.rights.none.fl_str_mv cc-by (c)Authors, 2021
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by (c)Authors, 2021
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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