Influence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patients
Abstract Nephrosclerosis patients are at an exceptionally high cardiovascular (CV) risk. We aimed to determine whether genetic variability represented by 38 tag-SNPs in genes of the cyclooxygenase pathway (PTGS1, PTGS2, PTGES, PTGES2 and PTGES3) leading to prostaglandin E2 (PGE2) synthesis, modified...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-27343-z |
| _version_ | 1811175906701475840 |
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| author | Luz M. González Nicolás R. Robles Sonia Mota-Zamorano José M. Valdivielso Laura González-Rodríguez Juan López-Gómez Guillermo Gervasini |
| author_facet | Luz M. González Nicolás R. Robles Sonia Mota-Zamorano José M. Valdivielso Laura González-Rodríguez Juan López-Gómez Guillermo Gervasini |
| author_sort | Luz M. González |
| collection | DOAJ |
| description | Abstract Nephrosclerosis patients are at an exceptionally high cardiovascular (CV) risk. We aimed to determine whether genetic variability represented by 38 tag-SNPs in genes of the cyclooxygenase pathway (PTGS1, PTGS2, PTGES, PTGES2 and PTGES3) leading to prostaglandin E2 (PGE2) synthesis, modified CV traits and events in 493 nephrosclerosis patients. Additionally, we genotyped 716 controls to identify nephrosclerosis risk associations. The addition of three variants, namely PTGS2 rs4648268, PTGES3 rs2958155 and PTGES3 rs11300958, to a predictive model for CV events containing classic risk factors in nephrosclerosis patients, significantly enhanced its statistical power (AUC value increased from 78.6 to 87.4%, p = 0.0003). Such increase remained significant after correcting for multiple testing. In addition, two tag-SNPs (rs11790782 and rs2241270) in PTGES were linked to higher systolic and diastolic pressure [carriers vs. non-carriers = 5.23 (1.87–9.93), p = 0.03 and 5.9 (1.87–9.93), p = 0.004]. PTGS1(COX1) rs10306194 was associated with higher common carotid intima media thickness (ccIMT) progression [OR 1.90 (1.07–3.36), p = 0.029], presence of carotid plaque [OR 1.79 (1.06–3.01), p = 0.026] and atherosclerosis severity (p = 0.041). These associations, however, did not survive Bonferroni correction of the data. Our findings highlight the importance of the route leading to PGE2 synthesis in the CV risk experienced by nephrosclerosis patients and add to the growing body of evidence pointing out the PGE2 synthesis/activity axis as a promising therapeutic target in this field. |
| first_indexed | 2024-04-10T19:44:40Z |
| format | Article |
| id | doaj.art-e2f9ee43073e4063a72b693a1ad151de |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-10T19:44:40Z |
| publishDate | 2023-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-e2f9ee43073e4063a72b693a1ad151de2023-01-29T12:09:13ZengNature PortfolioScientific Reports2045-23222023-01-0113111110.1038/s41598-022-27343-zInfluence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patientsLuz M. González0Nicolás R. Robles1Sonia Mota-Zamorano2José M. Valdivielso3Laura González-Rodríguez4Juan López-Gómez5Guillermo Gervasini6Department of Medical and Surgical Therapeutics, Medical School, University of ExtremaduraService of Nephrology, Badajoz University HospitalDepartment of Medical and Surgical Therapeutics, Medical School, University of ExtremaduraISCIII RICORS2040Department of Medical and Surgical Therapeutics, Medical School, University of ExtremaduraService of Clinical Analyses, Badajoz University HospitalDepartment of Medical and Surgical Therapeutics, Medical School, University of ExtremaduraAbstract Nephrosclerosis patients are at an exceptionally high cardiovascular (CV) risk. We aimed to determine whether genetic variability represented by 38 tag-SNPs in genes of the cyclooxygenase pathway (PTGS1, PTGS2, PTGES, PTGES2 and PTGES3) leading to prostaglandin E2 (PGE2) synthesis, modified CV traits and events in 493 nephrosclerosis patients. Additionally, we genotyped 716 controls to identify nephrosclerosis risk associations. The addition of three variants, namely PTGS2 rs4648268, PTGES3 rs2958155 and PTGES3 rs11300958, to a predictive model for CV events containing classic risk factors in nephrosclerosis patients, significantly enhanced its statistical power (AUC value increased from 78.6 to 87.4%, p = 0.0003). Such increase remained significant after correcting for multiple testing. In addition, two tag-SNPs (rs11790782 and rs2241270) in PTGES were linked to higher systolic and diastolic pressure [carriers vs. non-carriers = 5.23 (1.87–9.93), p = 0.03 and 5.9 (1.87–9.93), p = 0.004]. PTGS1(COX1) rs10306194 was associated with higher common carotid intima media thickness (ccIMT) progression [OR 1.90 (1.07–3.36), p = 0.029], presence of carotid plaque [OR 1.79 (1.06–3.01), p = 0.026] and atherosclerosis severity (p = 0.041). These associations, however, did not survive Bonferroni correction of the data. Our findings highlight the importance of the route leading to PGE2 synthesis in the CV risk experienced by nephrosclerosis patients and add to the growing body of evidence pointing out the PGE2 synthesis/activity axis as a promising therapeutic target in this field.https://doi.org/10.1038/s41598-022-27343-z |
| spellingShingle | Luz M. González Nicolás R. Robles Sonia Mota-Zamorano José M. Valdivielso Laura González-Rodríguez Juan López-Gómez Guillermo Gervasini Influence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patients Scientific Reports |
| title | Influence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patients |
| title_full | Influence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patients |
| title_fullStr | Influence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patients |
| title_full_unstemmed | Influence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patients |
| title_short | Influence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patients |
| title_sort | influence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patients |
| url | https://doi.org/10.1038/s41598-022-27343-z |
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