Polymorphisms in genes involved in vasoactive eicosanoids synthesis affect cardiovascular risk in renal transplant recipients

<p><b>Objective:</b> Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases lead to epoxyeicosatrienoic acids (EETs), which eicosanoids with vasodilator and anti-inflammatory properties. We aim to determine whether genetic variability in these routes may contribute to cardiovascular (CV) risk in renal transplant recipients.</p> <p><b>Methods:</b> In a cohort of 355 patients, we determined the presence of two polymorphisms, <i>CYP2C8*3</i> and <i>CYP2J2*7</i>, known to affect eicosanoids levels. Associations with CV mortality, CV event-free long-term survival and graft survival were retrospectively investigated by logistic regression models.</p> <p><b>Results:</b><i>CYP2J2*7</i> showed a statistical trend towards higher CV mortality (p = 0.06) and lower cardiac or cerebral event-free long-term survival (p = 0.05), whilst <i>CYP2C8*3</i> displayed a significant inverse association with the risk of CV event [HR = 0.34 (0.15-0.78), p = 0.01]. The association of <i>CYP2J2*7</i> with CV mortality became significant when the analysis was restrained to 316 patients without a history of CV events prior to transplantation [Hazard ratio (HR)=15.72 (2.83-91.94), p = 0.005]. In this subgroup of patients both SNPs were significantly associated with event-free survival. HR values were 5.44 (1.60-18.51), p = 0.007 and 0.26 (0.09-0.75), p = 0.012 for <i>CYP2J2*7</i> and <i>CYP2C8*3</i>, respectively.</p> <p><b>Conclusions:</b> Our results show, for the first time to our knowledge, that two SNPs in <i>CYP2C8</i> and <i>CYP2J2</i>, which synthesize EETs, may modify CV outcomes in renal transplant recipients, a population that is already at a high risk of suffering these events.</p>