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Article

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

1
Department of Medical and Surgical Therapeutics, Division of Pharmacology, Medical School, University of Extremadura, 06006 Badajoz, Spain
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Service of Nephrology, Badajoz University Hospital, 06080 Badajoz, Spain
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Vascular and Renal Translational Research Group, UDETMA, ISCIII REDinREN, IRBLleida, 25198 Lleida, Spain
4
Service of Clinical Analyses, Badajoz University Hospital, 06080 Badajoz, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Francesca Ariani
J. Pers. Med. 2021, 11(8), 772; https://doi.org/10.3390/jpm11080772
Received: 3 June 2021 / Revised: 2 August 2021 / Accepted: 4 August 2021 / Published: 6 August 2021
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. View Full-Text
Keywords: nephrosclerosis; PGE2; EP receptors; cardiovascular risk nephrosclerosis; PGE2; EP receptors; cardiovascular risk
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MDPI and ACS Style

González, L.M.; Robles, N.R.; Mota-Zamorano, S.; Valdivielso, J.M.; López-Gómez, J.; Gervasini, G. Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients. J. Pers. Med. 2021, 11, 772. https://doi.org/10.3390/jpm11080772

AMA Style

González LM, Robles NR, Mota-Zamorano S, Valdivielso JM, López-Gómez J, Gervasini G. Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients. Journal of Personalized Medicine. 2021; 11(8):772. https://doi.org/10.3390/jpm11080772

Chicago/Turabian Style

González, Luz M., Nicolás R. Robles, Sonia Mota-Zamorano, José M. Valdivielso, Juan López-Gómez, and Guillermo Gervasini. 2021. "Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients" Journal of Personalized Medicine 11, no. 8: 772. https://doi.org/10.3390/jpm11080772

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