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

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-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 SLCO1B3 T334G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)mg·h·L-1(P=0.052);SLCO1B1 A338G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>0.05).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.

Abstract：

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 (SLCO1B3T334G, 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.

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

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 (SLCO1B3T334G, 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.