Correlation between increasing tacrolimus concentration by Wuzhi Capsule and CYP3A5 gene polymorphism in donor liver
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摘要: 目的 探讨肝移植受者术后使用五酯胶囊提升他克莫司浓度与供肝CYP3A5基因多态性是否存在相关性。方法 肝移植术后，40例连续服用五酯胶囊6个月的患者为试验组，46例未服用五酯胶囊患者为对照组，计算在术后15 d、1个月、3个月、6个月时他克莫司C0/D值。同时，采用PCR-RFLP(聚合酶链反应)方法对CYP3A5基因型进行检测。结果 不考虑供肝CYP3A5基因情况下，在各时间点试验组与对照组他克莫司C0/D值比较，差异有统计学意义(P< 0.05)。供肝CYP3A5基因为1/1型和1/3型患者中，五酯胶囊能显著提高各时间点他克莫司C0/D值(P< 0.01)；但在CYP3A5 3/3型中，五酯胶囊对他克莫司C0/D值未见明显影响(P>0.05)。结论 五酯胶囊提升FK506血药浓度与供肝CYP3A5基因多态性有显著相关性。当使用五酯胶囊作为他克莫司的增效剂时，应该考虑CYP3A5基因多态性。Abstract: Objective To investigate whether the use of Wuzhi Capsule to increase the concentration of tacrolimus in liver transplant recipients is related to the CYP3A5 gene polymorphism of donor liver.Methods After liver transplantation, 40 patients who took Wuzhi Capsule for 6 months as the experimental group and 46 patients who did not take Wuzhi Capsule as the control group. The C0/D value of tacrolimus was calculated at 15 days, 1 month, 3 months and 6 months after operation. At the same time, the CYP3A5 genotype was detected by PCR-RFLP.Results Without considering the CYP3A5 gene of donor liver, there was significant difference in the C0/D value of tacrolimus between the experimental group and the control group at each time(P< 0.05). Among the patients with CYP3A5 gene type 1/1 and 1/3 of donor liver, Wuzhi Capsule could significantly increase the C0/D value of tacrolimus at each time point(P< 0.01); in gene type 3/3, Wuzhi Capsule had no significant effect on the C0/D value of tacrolimus(P>0.05).Conclusion There was a significant correlation between the increase of FK506 concentration by Wuzhi Capsule and the CYP3A5 gene polymorphism of donor liver. CYP3A5 gene polymorphism should be considered when Wuzhi Capsule is used as a synergist of tacrolimus.
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Key words:
- liver transplantation /
- Wuzhi Capsule /
- tacrolimus /
- donor liver /
- CYP3A5 /
- gene polymorphism
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表 1 五酯胶囊对FK506血药浓度的影响
X±S 组别 例数 C0/D 术后15 d 术后1个月 术后3个月 术后6个月 五脂胶囊(+) 40 1.74±0.31 1.79±0.23 1.86±0.19 2.03±0.22 五脂胶囊(-) 46 1.34±0.29 1.41±0.33 1.49±0.24 1.55±0.19 P < 0.05 < 0.05 < 0.05 < 0.05 
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表 2 CYP3A5基因型对五酯胶囊提升FK506浓度的影响
X±S 基因型 分组 例数 C0/D 术后15 d 术后1个月 术后3个月 术后6个月 1/1+1/3 五脂胶囊(+) 17 2.07±0.281) 2.15±0.211) 2.32±0.181) 2.43±0.241) 五脂胶囊(-) 21 1.09±0.19 1.16±0.32 1.22±0.27 1.28±0.21 3/3 五脂胶囊(+) 23 1.65±0.41 1.72±0.34 1.79±0.19 1.88±0.25 五脂胶囊(-) 25 1.56±0.25 1.63±0.19 1.76±0.31 1.81±0.28 与1/1+1/3基因型五脂胶囊(-)组比较，1)P＜0.01。
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