Association Research between CYP3A5，CYP3A4，ABCB1 and POR*28 Genetic Polymorphisms and Individualized Use of Tacrolimus in Lung Transplant Recipients after One Year of Tacrolimus Administration / 中国药房

ABSTRACT

ABSTRACT OBJECTIVE：To study the association between CYP3A5，CYP3A4，ABCB1 and POR*28 genetic polymorphisms and drug dosage（D）and steady blood concentration/dosage（c0/D）of tacrolimus in lung transplant recipients after one year of tacrolimus administration. METHODS：By retrospective analysis，a total of 46 recipients who underwent lung transplantation in China-Japan Friendship Hospital during May 2017-May 2018 were selected. The c0 and D of tacrolimus were measured and collected after one year of tacrolimus administration，and c0/D was calculated. Recipients’genotypes of CYP3A5（rs776746）， CYP3A4（rs2242480，rs28371759），ABCB1（rs1045642，rs2032582，rs1128503）and POR*28（rs1057868）were collected. The relationship between genetic polymorphism and D，c0/D was analyzed statistically. RESULTS：The genotype frequency in this study were all in accordance with Hardy-Weinberg equilibrium （P＞0.05）. While maintaining tacrolimus c0 within therapeutic range， genetic polymorphism of CYP3A5（rs776746）and CYP3A4（rs2242480）influenced D and c0/D of tacrolimus significantly（P＜ 0.05）. There was no statistical significance in D or c0/D among different genotypes of other sites（P＞0.05）. There was statistical significance in D or c0/D among extensive metabolism type recipients with CYP3A5（rs776746）*1 and CYP3A4（rs2242480）*1G alleles，normal metabolism type recipients with only CYP3A5 （rs776746） *1 or CYP3A4 （rs2242480） *1G alleles and poor metabolism type recipients without CYP3A5（rs776746）*1 and CYP3A4（rs2242480）* 1G alleles（P＜0.05）. D of tacrolimus was the highest in extensive metabolism type recipient and the lowest in poor metabolism type recipient. CONCLUSIONS：The detection of genetic polymorphism of CYP3A5（rs776746）and CYP3A4（rs2242480）has guiding significance for individualized medication of tacrolimus after one year of tacrolimus administration.