Impact of secondary pulmonary hypertension on lung transplant outcome / 中华器官移植杂志

ABSTRACT

Objective:To explore the effect of MDR1(C3435T) gene polymorphism on tacrolimus metabolism early after pediatric liver transplantation.Methods:Preoperative blood samples of 90 donors and recipients of pediatric liver transplantation were collected and genotyped. According to the CYP3A5 genotype of donor/recipient, they were divided into four subgroups of recipient slow metabolism/donor slow metabolism (R/D-S), recipient fast metabolism/donor slow metabolism (R-F/D-S), recipient slow metabolism/donor fast metabolism (R-S/D-F) and recipient fast metabolism/donor fast metabolism (R/D-F). The values of concentration/daily dose (C 0/D) of tacrolimus in patients with different MDR1 genotypes were compared at the subgroup level. Results:The C 0/D value of MDR1 TT recipients was significantly higher than that of CC/ CT counterparts in the first week after liver transplantation ( P<0.01). The C 0/D value of CT recipients in R/D-S subgroup was significantly higher than that of CC counterparts in the 2nd week after operation ( P<0.05). The C 0/D value of CT recipients in R/D-F subgroup was significantly higher than that of CC counterparts in 2 weeks ( P<0.05) and 3 weeks ( P<0.01). Conclusions:MDR1(C3435T) gene polymorphism in recipients affects tacrolimus metabolism. Recipients with CC genotype metabolize faster than those with CT/TT genotypes. And the same daily dose and tacrolimus blood concentration are lower. Recipients with different MDR1 genotypes need to adjust the dosage of tacrolimus. This difference is more obvious in CYP3A5 fast metabolic subgroup, more attention should be paid to optimizing individualizing dosage regimens, reducing the incidence of adverse reactions and improving the efficacy.