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

Association of synergistic effects of Wuzhi capsules on tacrolimus and PXR polymorphisms

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PXR24381 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C_0。采用协方差分析考察不同组别他克莫司C_0/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C_0/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 7635G>A GG型患者他克莫司C_0/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 7635G>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PXR7635 G>A基因多态性可能相关。

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-di- rect 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.