孕烷X受体基因多态性与五酯胶囊对他克莫司增效作用的相关性研究

摘要/Abstract

摘要：

目的: 研究肾移植患者中五酯胶囊对他克莫司增效作用与孕烷X受体（PXR）基因多态性的相关性。方法: 连续服用五酯胶囊24个月的患者74人为五酯胶囊（＋）组，未服用五酯胶囊的患者96人为五酯胶囊（－）组。通过直接测序法测定PXR 7635 G>A(rs6785049)和PXR 24381 C>A(rs1523127)基因型；通过等位基因特异性聚合酶链反应（ASPCR）方法测定PXR 6碱基缺失（rs3842689）基因型。使用化学发光微粒子免疫分析技术（CMIA）检测他克莫司C₀。采用协方差分析考察不同组别他克莫司C₀/D的差异。结果: 无论他克莫司是否与五酯胶囊联合使用，PXR 6碱基缺失以及PXR 24381 C>A不同基因型他克莫司C₀/D均无统计学差异。在五酯胶囊（＋）组中，用药3个月~24个月时，PXR 7635 G>A GG型患者他克莫司C₀/D与GA/AA型差异比较，有统计学意义（P=0.005、0.049、0.001、0.031、0.035），在五酯胶囊（－）组中，PXR 7635 G>A不同基因型他克莫司C0/D无统计学差异。结论: 五酯胶囊对他克莫司的增效作用与PXR 7635 G>A基因多态性可能相关。

关键词: 孕烷X受体, 基因多态性, 五酯胶囊, 他克莫司, 肾移植

Abstract:

AIM: To investigate the association of synergistic effects of Wuzhi capsules on tacrolimus and PXR polymorphisms. METHODS: A total of 74 patients were continually administered with Wuzhi capsules for 24 months as Wuzhi capsules (+) group. A total of 96 patients took tacrolimus alone as Wuzhi capsules (－) group. The PXR 7635 A>G (rs6785049) and PXR 24381 A>C (rs1523127) genotypes were determined by PCR-direct sequencing. PXR 6bp deletions (rs3842689) genotype was determined by Allelic Special-Touch down PCR. The tacrolimus whole blood levels of renal transplant recipients were measured by chemiluminescent microparticle immunoassay.Analysis of covariance (ANCOVA) was performed to determine the difference of tacrolimus C0/D among various groups. RESULTS: Tacrolimus C0/D of patients with PXR 7635 A>G GG was significantly higher than that with GA/AA in Wuzhi capsules (+) group from 3 months to 24 months (P=0.005, 0.049, 0.001, 0.031, 0.035) and there was no significant difference in Wuzhi capsule (－) group. Whether co-administration of Wuzhi capsules and tacrolimus or not, PXR 6bp deletions, PXR 24381 A>C genotype were not associated with tacrolimus C0/D.CONCLUSION:When combined with Wuzhi capsules, PXR 7635 G>A mutation might associate with tacrolimus C0/D.

Key words: PXR, genic polymorphism, Wuzhi capsules, tacrolimus, renal transplantation

中图分类号:

R968

辛华雯，杨燕. 孕烷X受体基因多态性与五酯胶囊对他克莫司增效作用的相关性研究[J]. 中国临床药理学与治疗学, 2017, 22(10): 1138-1144.

XIN Huawen, YANG Yan. Association of synergistic effects of Wuzhi capsules on tacrolimus and PXR polymorphisms[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(10): 1138-1144.

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