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 (<i>PTGER1-4</i>) and study associations with nephrosclerosis risk and clinical outcomes. We identified 96 tag-SNPs capturing global variabilit...
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doaj-92c418ca87b04523a35d62b8e0b09e6d2021-08-26T13:57:55ZengMDPI AGJournal of Personalized Medicine2075-44262021-08-011177277210.3390/jpm11080772Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These PatientsLuz María González0Nicolás Roberto Robles1Sonia Mota-Zamorano2José Manuel Valdivielso3Juan López-Gómez4Guillermo Gervasini5Department of Medical and Surgical Therapeutics, Division of Pharmacology, Medical School, University of Extremadura, 06006 Badajoz, SpainService of Nephrology, Badajoz University Hospital, 06080 Badajoz, SpainDepartment of Medical and Surgical Therapeutics, Division of Pharmacology, Medical School, University of Extremadura, 06006 Badajoz, SpainVascular and Renal Translational Research Group, UDETMA, ISCIII REDinREN, IRBLleida, 25198 Lleida, SpainService of Clinical Analyses, Badajoz University Hospital, 06080 Badajoz, SpainDepartment of Medical and Surgical Therapeutics, Division of Pharmacology, Medical School, University of Extremadura, 06006 Badajoz, SpainProstaglandin E2 (PGE2) is a major actor mediating renal injury. We aimed to determine genetic variability in the genes coding for its receptors (<i>PTGER1-4</i>) and study associations with nephrosclerosis risk and clinical outcomes. We identified 96 tag-SNPs capturing global variability in <i>PTGER1-4</i> and screened 1209 nephrosclerosis patients and controls. The effect of these variants was evaluated by multivariate regression analyses. Two <i>PTGER3</i> SNPs, rs11209730 and rs10399704, remained significant in a backward elimination regression model with other non-genetic variables (OR = 1.45 (1.07–1.95), <i>p</i> = 0.016 and OR = 0.71 (0.51–0.99), <i>p</i> = 0.041, respectively). In the nephrosclerosis patients, a proximal region of <i>PTGER3</i> was tagged as relevant for eGFR (<i>p</i> values for identified SNPs ranged from 0.0003 to 0.038). Two consecutive <i>PTGER3</i> SNPs, rs2284362 and rs2284363, significantly decreased systolic (<i>p</i> = 0.005 and <i>p</i> = 0.0005), diastolic (<i>p</i> = 0.039 and <i>p</i> = 0.005), and pulse pressure values (<i>p</i> = 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 <i>PTGER1</i>rs2241360 T variant had better CV event-free survival than wild-type individuals (<i>p</i> = 0.029). In addition, <i>PTGER3</i>rs7533733 GG carriers had lower event-free survival than AA/AG patients (<i>p</i> = 0.011). Our results indicate that genetic variability in PGE2 receptors, particularly EP3, may be clinically relevant for nephrosclerosis and its associated CV risk.https://www.mdpi.com/2075-4426/11/8/772nephrosclerosisPGE2EP receptorscardiovascular risk |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Luz María González Nicolás Roberto Robles Sonia Mota-Zamorano José Manuel Valdivielso Juan López-Gómez Guillermo Gervasini |
spellingShingle |
Luz María González Nicolás Roberto Robles Sonia Mota-Zamorano José Manuel Valdivielso Juan López-Gómez Guillermo Gervasini Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients Journal of Personalized Medicine nephrosclerosis PGE2 EP receptors cardiovascular risk |
author_facet |
Luz María González Nicolás Roberto Robles Sonia Mota-Zamorano José Manuel Valdivielso Juan López-Gómez Guillermo Gervasini |
author_sort |
Luz María González |
title |
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_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 |
publisher |
MDPI AG |
series |
Journal of Personalized Medicine |
issn |
2075-4426 |
publishDate |
2021-08-01 |
description |
Prostaglandin E2 (PGE2) is a major actor mediating renal injury. We aimed to determine genetic variability in the genes coding for its receptors (<i>PTGER1-4</i>) and study associations with nephrosclerosis risk and clinical outcomes. We identified 96 tag-SNPs capturing global variability in <i>PTGER1-4</i> and screened 1209 nephrosclerosis patients and controls. The effect of these variants was evaluated by multivariate regression analyses. Two <i>PTGER3</i> SNPs, rs11209730 and rs10399704, remained significant in a backward elimination regression model with other non-genetic variables (OR = 1.45 (1.07–1.95), <i>p</i> = 0.016 and OR = 0.71 (0.51–0.99), <i>p</i> = 0.041, respectively). In the nephrosclerosis patients, a proximal region of <i>PTGER3</i> was tagged as relevant for eGFR (<i>p</i> values for identified SNPs ranged from 0.0003 to 0.038). Two consecutive <i>PTGER3</i> SNPs, rs2284362 and rs2284363, significantly decreased systolic (<i>p</i> = 0.005 and <i>p</i> = 0.0005), diastolic (<i>p</i> = 0.039 and <i>p</i> = 0.005), and pulse pressure values (<i>p</i> = 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 <i>PTGER1</i>rs2241360 T variant had better CV event-free survival than wild-type individuals (<i>p</i> = 0.029). In addition, <i>PTGER3</i>rs7533733 GG carriers had lower event-free survival than AA/AG patients (<i>p</i> = 0.011). Our results indicate that genetic variability in PGE2 receptors, particularly EP3, may be clinically relevant for nephrosclerosis and its associated CV risk. |
topic |
nephrosclerosis PGE2 EP receptors cardiovascular risk |
url |
https://www.mdpi.com/2075-4426/11/8/772 |
work_keys_str_mv |
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