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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 principales: González, Luz María, Robles, Nicolás Roberto, Mota-Zamorano, Sonia, Valdivielso, José Manuel, López-Gómez, Juan, Gervasini, Guillermo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400263/
https://www.ncbi.nlm.nih.gov/pubmed/34442416
http://dx.doi.org/10.3390/jpm11080772
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author González, Luz María
Robles, Nicolás Roberto
Mota-Zamorano, Sonia
Valdivielso, José Manuel
López-Gómez, Juan
Gervasini, Guillermo
author_facet González, Luz María
Robles, Nicolás Roberto
Mota-Zamorano, Sonia
Valdivielso, José Manuel
López-Gómez, Juan
Gervasini, Guillermo
author_sort González, Luz María
collection PubMed
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.
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spelling pubmed-84002632021-08-29 Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients González, Luz María Robles, Nicolás Roberto Mota-Zamorano, Sonia Valdivielso, José Manuel López-Gómez, Juan Gervasini, Guillermo J Pers Med Article 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. MDPI 2021-08-06 /pmc/articles/PMC8400263/ /pubmed/34442416 http://dx.doi.org/10.3390/jpm11080772 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
González, Luz María
Robles, Nicolás Roberto
Mota-Zamorano, Sonia
Valdivielso, José Manuel
López-Gómez, Juan
Gervasini, Guillermo
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400263/
https://www.ncbi.nlm.nih.gov/pubmed/34442416
http://dx.doi.org/10.3390/jpm11080772
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