Risk factors for post-transplant diabetes mellitus in renal transplant: Role of genetic variability in the CYP450-mediated arachidonic acid metabolism.

摘要: Arachidonic acid (AA) is metabolized by cytochrome P450 (CYP) enzymes to epoxyeicosatrienoic acids (EETs) and 20-hidroxyeicosatetraenoic (20-HETE), which play an important role both in renal transplant diabetes mellitus (DM). We searched for associations between polymorphisms this metabolic pathway the risk of post-transplant (PTDM) kidney recipients. One-hundred-sixty-four patients were genotyped common SNPs route, namely CYP2C8*3, CYP2C8*4, CYP2C9*2, CYP2C9*3, CYP2J2*7, CYP4A11 F434S CYP4F2 V433M. Demographic clinical parameters retrospectively collected at four time-points first year after grafting. Thirty-four (20.73%) developed PTDM, was more prevalent among older [OR age = 1.06 (1.03-1.10), p < 0.001] those with higher body mass index (BMI) average BMI 1.13 (1.04-1.23); 0.01]. Creatinine clearance 0.97 (0.95-0.99); 0.01] exposure tacrolimus 3.25 (1.15-9.19); 0.05] also relevant PTDM risk. With regard genetic variants, logistic regression analysis controlling significant demographic variables showed that V433M polymorphism CYP4F2, responsible 20-HETE synthesis, independent factor 3.94 (1.08-14.33); 0.05]. have shown a variant gene, main gene implicated associated PTDM. Our findings suggest genes pathways AA may become good candidates association studies