Polymorphisms in CYP-mediated arachidonic acid routes affect the outcome of renal transplantation

摘要: Background Arachidonic acid (AA) is metabolized by cytochrome P450 (CYP) enzymes to vasoactive metabolites (mainly epoxyeicosatrienoic acids) which are known play a protective role against damaging processes that may occur after re-oxygenation of the graft. We aimed investigate whether presence functional polymorphisms along these metabolic routes in outcome renal transplantation. Design One-hundred and forty Caucasian transplant recipients 137 donors were included. determined seven common five genes governing CYP-mediated AA pathway (CYP2C8, CYP2C9, CYP2J2, CYP4A11 CYP4F2). Associations with parameters events related graft function survival retrospectively investigated throughout first year grafting. Results The CYP2J2*7 allele donor was significantly associated higher risk for delayed [OR = 4·40 (1·45–13·37), P < 0·01] lower death-censored [107·90 (84·19–131·62) vs. 176·89 (166·47–187·32) months CYP2J2*1/*1 grafts; log-rank P = 0·015]. In addition, patients whose carried 434S variant F434S polymorphism displayed impaired creatinine clearance, statistically significant differences 434FF subjects whole period study (P < 0·05, P < 0·01, P < 0·001 P < 0·05 1 week, 1 month, 5 months 1 year grafting, respectively). Conclusions Taken together, results indicate variability CYP450 involved synthesis eicosanoids from have impact on transplantation.