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
- VernacularTitle:肺移植患者术后使用他克莫司1年CYP3A5、CYP3A4、ABCB1、POR*28基因多态性与他克莫司个体化用药的关系研究
- Author:
Wenwen DU
1
;
Xiaoxing WANG
1
;
Dan ZHANG
1
;
Pengmei LI
1
Author Information
1. Dept. of Pharmacy,China-Japan Friendship Hospital,Beijing 100029,China
- Publication Type:Journal Article
- Keywords:
Tacrolimus;
Geng polymorphism;
Lung transplant;
One year after operation;
Blood concentration;
Drug dosage
- From:
China Pharmacy
2020;31(1):80-85
- CountryChina
- Language:Chinese
-
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.