In order to investigate the relationship between a functional gene polymorphism (Q192R) of paraoxonase 1 (PON1) with markers of systemic oxidative stress and cardiovascular risk, the association between PON1 activity measures, polymorphism, and future major adverse cardiac events (MACE) was assessed in 1,399 patients undergoing diagnostic coronary angiography. Compared to individuals with either the RR192 or QR192 genotypes, individuals with the QQ192 genotype had an adjusted hazard ratio of 2.05 (95% CI, 1.32-3.18) for mortality and 1.48 (95% CI, 1.09-2.03) for MACE. This genotype was also associated with decreased serum PON1 levels and activity while being positively associated with increased levels of systemic indices of oxidative stress. Given the importance of oxidative stress in several chronic inflammatory diseases including atherosclerosis, these findings underline the importance of PON1 and of a functional polymorphism associated with its serum levels and activity as an important mediator of the relationship between oxidative stress and associated mortality and MACE incidence.
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