Paraoxonase Variants Relate to 10-Year Risk in Coronary Artery Disease
| Autor: | Diederick E. Grobbee, Aeilko H. Zwinderman, John J.P. Kastelein, Jakub J. Regieli, Pieter A. Doevendans, J. Wouter Jukema, Yolanda van der Graaf |
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| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Statin biology Vascular disease business.industry Proportional hazards model medicine.drug_class Hazard ratio Paraoxonase Bioinformatics medicine.disease Coronary artery disease Endocrinology Internal medicine Relative risk medicine biology.protein Risk factor business Cardiology and Cardiovascular Medicine |
| Zdroj: | Journal of the American College of Cardiology. 54(14):1238-1245 |
| ISSN: | 0735-1097 |
| DOI: | 10.1016/j.jacc.2009.05.061 |
| Popis: | Objectives We investigated the effects of paraoxonase (PON)-1 variants on long-term clinical outcome in patients with coronary artery disease (CAD). Background PON-1 is a potential therapeutic target to further reduce cardiovascular risk because it is a detoxifying esterase with antioxidant properties. The PON-1 knockout models result in higher susceptibility to atherosclerosis, and PON activity contributes to cardiovascular risk in humans. Human gene variants determine PON activity; however, the impact of these variants on recurrent cardiovascular events in vascular disease is as of yet unknown. Methods We conducted a 10-year follow-up study of 793 CAD patients in the REGRESS (REgression GRowth Evaluation Statin Study) trial cohort, using nationwide registries. Genotypes were obtained of 2 PON-1 isotypes (L55M, rs854560, and Q192R, rs662), which were previously associated with PON activity. Absolute and relative risks by genotype were estimated using Kaplan-Meier and proportional hazards analyses. Results Carriership of the PON-1 glutamine isotype at codon 192 and methionine at codon 55 was associated with a higher risk of death due to ischemic heart disease. Hazard ratios per allele copy were 1.71 (95% confidence interval: 1.0 to 2.8, p = 0.03) for the glutamine isotype at codon 192 and 1.56 (95% confidence interval: 1.1 to 2.3, p = 0.03) for methionine at codon 55. Both isotypes had previously been related to lower PON activity. No effect was observed on all-cause mortality. Conclusions PON-1 gene variants influence the 10-year risk of fatal complications from CAD in male patients, despite no effect on all-cause mortality. These long-term findings confirm functional data on PON-1 activity, emphasize the relevance of this pathway in vascular disease, and enforce its putative role as a target to modify and estimate cardiovascular risk. |
| Databáze: | OpenAIRE |
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