CAJ | 학술논문

背景:多药耐药基因1 C3435T 基因多态性影响着 P-糖蛋白的功能和表达,从而影响环孢素 A 血药浓度,产生个体差异.目前多药耐药基因1 C3435T 基因多态性对环孢素 A 药物动力学影响的研究结果不一.目的:基于国内外报道的国内相关研究,系统评价多药耐药基因1 C3435T 基因多态性与环孢素 A 药物动力学的关系.方法:计算机检索 Cochrane 图书馆、Medline、Plumbed、CNKI、万方等数据库,并辅以文献追溯的方法,收集国内外公开发表的国内相关病例对照、队列研究.检索年限均为从建库至2011-12-31.按纳入、排除标准筛选文献并评价纳入研究的质量后,采用 RevMan 5.1软件进行 Meta 分析.结果与结论:共纳入9篇文献,合计893例患者.Meta 分析结果表明,多药耐药基因1 3435CC 的环孢素 A 剂量调整谷浓度显著低于 CT 基因型(P=0.007)和 TT 基因型(P=0.0006);亚组分析显示,肾移植后患者多药耐药基因1 3435CC 的环孢素 A 剂量调整谷浓度显著低于 CT 基因型(P <0.00001)及 TT 基因型(P=0.0003);血液系统疾病患者多药耐药基因1 3435CC 的环孢素 A 剂量调整谷浓度显著低于 TT 基因型(P=0.004).多药耐药基因1 3435CC的环孢素 A 剂量调整峰浓度显著低于 TT 基因型(P=0.005).提示多药耐药基因1 C3435T 基因多态性对环孢素 A 血药浓度有影响,CC 基因型患者血药浓度低于 TT 基因型.还需要大样本、前瞻性研究来探讨多药耐药基因1 C3435T基因多态性与环孢素 A 药物动力学的关系.
배경:다약내약기인1 C3435T 기인다태성영향착 P-당단백적공능화표체,종이영향배포소 A 혈약농도,산생개체차이.목전다약내약기인1 C3435T 기인다태성대배포소 A 약물동역학영향적연구결과불일.목적:기우국내외보도적국내상관연구,계통평개다약내약기인1 C3435T 기인다태성여배포소 A 약물동역학적관계.방법:계산궤검색 Cochrane 도서관、Medline、Plumbed、CNKI、만방등수거고,병보이문헌추소적방법,수집국내외공개발표적국내상관병례대조、대렬연구.검색년한균위종건고지2011-12-31.안납입、배제표준사선문헌병평개납입연구적질량후,채용 RevMan 5.1연건진행 Meta 분석.결과여결론:공납입9편문헌,합계893례환자.Meta 분석결과표명,다약내약기인1 3435CC 적배포소 A 제량조정곡농도현저저우 CT 기인형(P=0.007)화 TT 기인형(P=0.0006);아조분석현시,신이식후환자다약내약기인1 3435CC 적배포소 A 제량조정곡농도현저저우 CT 기인형(P <0.00001)급 TT 기인형(P=0.0003);혈액계통질병환자다약내약기인1 3435CC 적배포소 A 제량조정곡농도현저저우 TT 기인형(P=0.004).다약내약기인1 3435CC적배포소 A 제량조정봉농도현저저우 TT 기인형(P=0.005).제시다약내약기인1 C3435T 기인다태성대배포소 A 혈약농도유영향,CC 기인형환자혈약농도저우 TT 기인형.환수요대양본、전첨성연구래탐토다약내약기인1 C3435T기인다태성여배포소 A 약물동역학적관계.
BACKGROUND: Multi-drug resistance gene-1 C3435T genetic polymorphism can influence the function and expression of P-glycoprotein, thus affecting the blood concentration of cyclosporine A, and lead to individual differences. The current studies of the influence of multi-drug resistance gene-1 C3435T genetic polymorphism on the concentration of cyclosporin A pharmacokinetics are inconsistent. OBJECTIVE: To evaluate the effect of multi-drug resistance gene-1 C3435T genetic polymorphism on the concentration of cyclosporine A pharmacokinetics according to the domestic studies. METHODS: Case-control studies and cohort studies were col ected by searching Cochrane library, Medline database, PubMed database, CNKI database and Wanfang database and supplemented by literature retrospective method from building to 2011-12-31. Al the relevant studies were identified and the quality of the included studies was assessed. The RevMan 5.1 software was used for Meta-analysis. RESULTS AND CONCLUSION: Nine studies with 893 patients were included. The results of Meta-analysis showed that the dose-adjusted c0 level of cyclosporine A of multi-drug resistance gene-1 3435CC genotype was lower than of the CT genotype (P=0.007) and TT genotype (P=0.000 6). The subgroup analysis found that the dose-adjusted c0 level of multi-drug resistance gene-1 3435CC genotype was lower than that of CT genotype (P < 0.000 01) and TT genotype (P=0.000 3) in the patients after renal transplantation. The dose-adjusted c0 level of multi-drug resistance gene-1 3435CC genotype was lower than that of TT genotype (P=0.004) in the patients with hematological diseases. The dose-adjusted c2 level of the multi-drug resistance gene-1 3435CC genotype was lower than that of the TT genotype (P=0.005). The multi-drug resistance gene-1 C3435T genetic polymorphism can influence the blood concentration of cyclosporine A, and the blood concentration of multi-drug resistance gene-1 3435CC genotype was lower than that of TT genotype. High quality and large scale prospective trials are required to study the influence of multi-drug resistance gene-1 C3435T genetic polymorphism on cyclosporine A pharmacokinetics.