發(fā)布時(shí)間：2018-03-30 17:42

  本文選題：他克莫司　切入點(diǎn)：VDR　出處：《藥學(xué)學(xué)報(bào)》2017年05期

【摘要】：通過回顧性研究,探討維生素D受體(VDR)的單核苷酸多態(tài)性(SNP)與腎移植術(shù)后早期患者體內(nèi)他克莫司全血谷濃度的相關(guān)性。共納入114例活體腎移植術(shù)后服用他克莫司+霉酚酸酯+糖皮質(zhì)激素的患者,采用Agena Bioscience Mass ARRAY~汶 system檢測(cè)VDR rs2853559和rs1540339基因型,采用PCR-RFLP法檢測(cè)CYP3A5*3基因型,術(shù)后第7天他克莫司全血谷濃度(C_0)為臨床治療藥物監(jiān)測(cè)(TDM)數(shù)據(jù),采用Spearman相關(guān)分析、Mann-Whitney U檢驗(yàn)、Kruskal-Wallis H檢驗(yàn)進(jìn)行數(shù)據(jù)分析。結(jié)果顯示,VDR基因rs2853559 GA+GG型他克莫司劑量校正谷濃度顯著高于AA型。以CYP3A5*3基因型進(jìn)行分層后,在CYP3A5非表達(dá)型組中VDR rs2853559 GA+GG型他克莫司劑量校正谷濃度顯著高于AA型�；貧w分析表明,CYP3A5*3及VDR rs2853559能解釋45.6%的他克莫司劑量校正谷濃度個(gè)體差異,在CYP3A5非表達(dá)者中,VDR rs2853559能解釋14.4%的他克莫司劑量校正谷濃度個(gè)體差異。腎移植術(shù)后患者VDR rs2853559基因多態(tài)性與他克莫司校正谷濃度相關(guān),該基因型檢測(cè)將有助于指導(dǎo)他克莫司的臨床個(gè)體化用藥。
[Abstract]:A retrospective study was conducted to investigate the association of single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) with the whole blood valley concentration of tacrolimus in the early stage of renal transplantation.The genotypes of VDR rs2853559 and rs1540339 were detected by Agena Bioscience Mass arrayven system and CYP3A5*3 genotypes were detected by PCR-RFLP method in 114 patients who were treated with tacrolimolic acid glucocorticoid after renal transplantation in vivo.On the 7th day after operation, tacrolimus whole blood valley concentration (C0) was used as clinical drug monitoring data. Spearman correlation analysis was used to analyze the data by Kruskal-Wallis H test with Mann-Whitney U test.The results showed that rs2853559 GA GG dosimetric correction valley concentration of VDR gene was significantly higher than that of AA type.After stratification with CYP3A5*3 genotype, the dosimetric correction valley concentration of VDR rs2853559 GA GG type tacrolimus was significantly higher than that of AA type in CYP3A5 non-expression group.The regression analysis showed that CYP3A5H3 and VDR rs2853559 could explain 45.6% of the individual differences in dosimetric corrected valley concentration of tacrolimus, and 14.4% of the nonexpressed CYP3A5 could explain the individual difference of tacrolimus dosimetric corrected valley concentration.The polymorphism of VDR rs2853559 gene is associated with tacrolimus corrected valley concentration in renal transplantation patients. This genotype detection will be helpful to guide tacrolimus in clinical individualized drug use.
【作者單位】： 中山大學(xué)藥學(xué)院臨床藥理研究所;中山大學(xué)附屬第一醫(yī)院器官移植科;中山大學(xué)腫瘤防治中心藥學(xué)部;
【基金】：“十二五”國家科技重大專項(xiàng)資助項(xiàng)目(2012ZX09506001-004) 國家自然科學(xué)基金資助項(xiàng)目(81102515,81320108027) 國家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目(2016YFC0905000) 廣東省重點(diǎn)實(shí)驗(yàn)室建設(shè)項(xiàng)目(2011A060901014) 廣東省重大科技專項(xiàng)(2011A080300001,2012A080202013)
【分類號(hào)】：R692

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