CYP3A4^＊ 1G、CYP3A5^＊ 3基因多态性对肾移植后高血压患者他克莫司血药浓度/剂量比的影响  

Effects of CYP3A4^＊ 1G and CYP3A5^＊ 3 polymorphism on the concentration/dose ratio of tacrolimus in renal transplant recipients with hypertension

作　　者：席兰艳[1,2] 袁洪[2] 明英姿[3] 朱利军[3] 阳国平[2] 谢和宾[4] 黄志军[2] 

机构地区：[1]长沙市中心医院药学部 [2]中南大学湘雅三医院临床药理中心 [3]卫生部移植医学工程技术研究中心 [4]长沙市中心医院院感科

出　　处：《中国临床药理学与治疗学》2015年第12期1382-1387,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(81273594;81202166);国家科技支撑计划(2012BAI37B05)

摘　　要：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.

关 键 词：他克莫司 细胞色素P-450 CYP3A 肾移植 高血压 基因多态性 

分 类 号：R969.1[医药卫生—药理学]