目的:探讨肾移植后高血压患者中CYP3A4^*1G、CYP3A5^*3基因多态性对他克莫司血药浓度/剂量比(C/D)的影响。方法:以70例肾移植后高血压患者为研究对象,使用PCRRFLP法和测序法检测患者CYP3A4^*1G、CYP3A5^*3基因型,患者连续服用他克莫司至少达3 d后,采用微粒子酶免疫分析法(MEIA)测定患者的他克莫司血药谷浓度(C0),比较CYP3A4^*1G和CYP3A5^*3基因多态性对患者他克莫司血药浓度/剂量比(C/D)的影响。结果:肾移植后高血压患者中,携带CYP3A4^*1G野生型(^*1^*1)患者的他克莫司C/D明显高于CYP3A4突变杂合子(^*1^*1G)和CYP3A4突变纯合子(^*1G^*1G)携带者(P〈0.05);CYP3A5^*3突变纯合子(^*3^*3)患者的他克莫司C/D明显高于CYP3A5野生型(^*1^*1)和CYP3A5突变杂合子(^*1^*3)基因型患者(P〈0.05)。要达到相同的目标血药浓度,CYP3A4^*1G的^*1^*1G和^*1G^*1G患者比^*1^*1患者需要更高剂量的他克莫司,CYP3A5^*3的^*1^*1和^*1^*3患者比^*3^*3患者需要更高剂量的他克莫司。结论:CYP3A4^*1G、CYP3A5^*3基因多态性与肾移植后高血压患者的他克莫司C/D显著相关。
AIM: To study the effects of CYP3A4^*1G and CYP3A5^*3 gene polymorphism on concentration / dose ratio( C / D) of tacrolimus.METHODS: Seventy patients with post renal transplant hypertension were screened in the study. Polymerase restrictive fragment length polymorphism( PCR-RFLP) and PCR sequencing PCR technique were used to detect the CYP3A4^*1G and CYP3A5^*3 gene polymorphism. Tacrolimus trough level( C0)was determined by microparticle enzyme immunoassay( MEIA) when tacrolimus was administrated at a stable dose for at least 3 days. RESULTS: Among the patients with post renal transplant hypertension,C / D of tacrolimus for patients with CYP3A4^*1^*1was higher than that of those with CYP3A4-*1-*1G and CYP3A4^*1G^*1G( P〈0. 05). C / D of tacrolimus for patients with CYP3A5^*3-*3 was higher than that of those CYP3A5^*1^*1 and CYP3A5^*1^*3( P〈0. 05). CYP3A4^*1^*1G and CYP3A4^*1G-*1G patients required higher dosage of tacrolimus than CYP3A4^*1^*1 patients,and CYP3A5^*1^*1 and CYP3A5-*1-*3 patients required higher dosage of tacrolimus than the CYP3A5^*3^*3 patients to get similar plasma tacrolimus concentration. CONCLUSION: C / D of tacrolimus is significantly associated with the CYP3A4^*1G and CYP3A5^*3 gene polymorphism.