有机阴离子转运体1B1和1B3基因多态性对肾移植受者血麦考酚酸浓度的影响

Influence of organic anion transporting potypeptide （SLCO1B1 and SLCO1B3） genetic polymorphisms on mycophenolic acid in Chinese kidney transplantation patients

目的探讨有机阴离子转运体1B1和1B3（编码基因分别为SLCO1B1和SLCO1B3）基因多态性对肾移植受者血麦考酚酸（MPA）浓度的影响。方法用聚合酶链反应一连接酶检测反应法对68例汉族肾移植受者的SLCO1B1和1B3基因进行单核苷酸基因多态性（SNP）检测，分别检测SLCO1B3 T334G和SLCO1B1 A338G的突变位点。术后第28天，收集受者血浆检测MPA浓度。比较各基因型受者的MPA浓度-时间曲线下面积（AUC0-12），分析单核苷酸多态性与MPA AUC0-12：之间的相关性。结果SLCO1B3T334G位点GG基因型受者的MPA AUG0-12高于TT基因型受者，分别为（54．54±14．40）mg·h·L^-1和（37．30±12．88）rng·h·L^-1（P=0．052）；SLC0181A338G位点的各个基因型受者之间MPA AUC0-12比较，差异均无统计学意义（P〉O．05）。结论SLCO1B3基因多态性对肾移植受者术后血MPA浓度的个体间差异产生明显影响。

Objective To analyze the relationship between the genetic polymorphisms of organic anion transporting polypeptide （SLCO1B1 and SLCO1B3 ） and mycophenolic acid （MPA） pharmacokinetics in Chinese kidney transplant recipients. Methods Gene mutations （SLCO1B3 T334G, SLCO1B1 A338G） were detected in 68 recipients by PCR-LDR The plasma samples were collected and blood concentration of MPA was measured on the 28 th day after transplantation. The area under the curve （AUC）0-12 of MPA in different genotype recipients was compared to analyze the correlation between single nucleotide polymorphisms （SNPs） and MPA pharmacokinetics. Results MPA AUC0-12 was higher in SLCO1B3 T334G GG carriers group than in TT carriers [（54. 54 ± 14. 40） vs （37. 30 ± 12. 88） mg·h·L^-1 , （P = 0. 052）]. However, there was no difference in MPA AUC0-12 among each genotype of SLCO1B1 A338G （P〉0. 05）. Conclusion Genetic polymorphisms of SLCO1B3 affect interindividual variety in plasma MPA concentration in Chinese kidney transplantation recipients.