Polymorphisms in genes involved in vasoactive eicosanoid synthesis affect cardiovascular risk in renal transplant...

Arachidonic acid metabolism by cytochrome P450 (CYP) epoxygenases leads to epoxyeicosatrienoic acids (EETs), which are 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.

In a cohort of 355 patients, we determined the presence of two polymorphisms, CYP2C8*3 and CYP2J2*7, known to affect eicosanoid levels. Associations with CV mortality, CV event-free long-term survival and graft survival were retrospectively investigated by logistic regression models.

CYP2J2*7 showed a statistical trend towards higher CV mortality (p = .06) and lower cardiac or cerebral event-free long-term survival (p = .05), whilst CYP2C8*3 displayed a significant inverse association with the risk of CV event (hazard ratio [HR] = 0.34 [0.15-0.78], p = .01). The association of CYP2J2*7 with CV mortality became significant when the analysis was restrained to 316 patients without a history of CV events prior to transplantation (HR = 15.72 [2.83-91.94], p = .005). In this subgroup of patients both single nucleotide polymorphisms (SNPs) were significantly associated with event-free survival. HR values were 5.44 (1.60-18.51), p = .007 and 0.26 (0.09-0.75), p = .012 for CYP2J2*7 and CYP2C8*3, respectively.

Our results show, for the first time to our knowledge, that two SNPs in CYP2C8 and CYP2J2, which synthesize EETs, may modify CV outcomes in renal transplant recipients, a population that is already at a high risk of suffering these events.