FMO3、ABCC1基因多态性及术前总胆固醇水平预测肝移植术后新发高血压OA

Objective To investigate the risk factors for new-onset hypertension(NOHP)after liver transplantation and its impact on recipient survival.Methods A total of 168 recipients who underwent orthotopic liver transplantation at Shanghai General Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2015 to December 2018 were retrospectively enrolled.Patients were divided into the NOHP group(n=26)and the non-NOHP group(n=142)based on the occurrence of NOHP after liver transplantation.Baseline characteristics were compared between the two groups.Genetic polymorphism analysis was performed by using a drug-metabolizing enzymes and transporters(DEMT)chip to screen genotypes significantly associated with NOHP,which were subsequently validated in the clinical cohort.Genotype,allele frequencies,and linkage disequilibrium were analyzed.Univariate and multivariate Logistic regression analyses were used to identify independent risk factors for NOHP and to construct a prediction model.The model's performance was evaluated using the receiver operating characteristic(ROC)curve and its area under the curve(AUC),calibration curve,and decision curve analysis(DCA).Survival curves were plotted using the Kaplan-Meier method and compared with the Log-rank test.The incidence of major postoperative complications was also analyzed.Results The incidence of NOHP was 15.5%.Compared with the non-NOHP group,the NOHP group had a higher prevalence of pre-transplant hyperlipidemia,higher pre-transplant total cholesterol and urea levels,and a higher incidence of new-onset diabetes mellitus(all P<0.05).Univariate and multivariate Logistic regression analyses identified donor FMO3 rs1800822 genotype(OR=3.276,95%CI 1.029 to 10.424,P=0.045),recipient ABCC1 rs212091 genotype(OR=0.333,95%CI 0.119 to 0.933,P=0.036),and pre-transplant total cholesterol level(OR=1.426,95%CI 1.084 to 1.877,P=0.011)as independent risk factors for NOHP.The AUC of the prediction model based on these factors was 0.724(95%CI 0.604 to 0.842,P<0.001).Prognostic analysis showed that NOHP did not affect the overall survival of recipients but significantly increased the risk of acute and chronic renal failure(P=0.002).Conclusion Donor FMO3 rs1800822 genotype,recipient ABCC1 rs212091 genotype,and pre-transplant total cholesterol level are independent risk factors for NOHP after liver transplantation.The prediction model based on these factors demonstrates good discriminative ability.NOHP does not affect the post-transplant survival rate of liver transplant recipients.