CAJ | 학술논문

目的：研究汉族人群多重耐药基因（ MDR1） C1236T、G2677T／A和C3435T基因多态性对肾移植患者他克莫司血药浓度／校正剂量比值的影响。方法用基因芯片法对101名健康志愿者和56例肾移植患者的 MDR1C1236T、G2677T／A和C3435T这3个位点进行基因多态性分型检测，随机选取50个位点进行DNA测序来验证基因芯片法。测定56例患者在术后7，14 d、1，3，6个月空腹服用他克莫司的血药浓度，比较不同基因型在该时段内的他克莫司血药浓度／校正剂量（ C／D）比值之间的差异。结果在健康志愿者样本人群中MDR1C1236T、G2677T／A、C3435T 的突变频率分别为43.05％，14.90％，40.10％，与本研究中的56例肾移植患者的突变频率基本一致，符合Hardy－Weinberg平衡。 MDR1C1236T、G2677T／A和C3435T的基因多态性在肾移植术后6个月内不同时间点他克莫司血药浓度／校正剂量比值比较差异均无统计学意义（P＞0.05）。结论 MDR1C1236T、G2677T／A和C3435T的基因多态性与肾移植患者服用他克莫司C／D比值无显著相关性。
목적：연구한족인군다중내약기인（ MDR1） C1236T、G2677T／A화C3435T기인다태성대신이식환자타극막사혈약농도／교정제량비치적영향。방법용기인심편법대101명건강지원자화56례신이식환자적 MDR1C1236T、G2677T／A화C3435T저3개위점진행기인다태성분형검측，수궤선취50개위점진행DNA측서래험증기인심편법。측정56례환자재술후7，14 d、1，3，6개월공복복용타극막사적혈약농도，비교불동기인형재해시단내적타극막사혈약농도／교정제량（ C／D）비치지간적차이。결과재건강지원자양본인군중MDR1C1236T、G2677T／A、C3435T 적돌변빈솔분별위43.05％，14.90％，40.10％，여본연구중적56례신이식환자적돌변빈솔기본일치，부합Hardy－Weinberg평형。 MDR1C1236T、G2677T／A화C3435T적기인다태성재신이식술후6개월내불동시간점타극막사혈약농도／교정제량비치비교차이균무통계학의의（P＞0.05）。결론 MDR1C1236T、G2677T／A화C3435T적기인다태성여신이식환자복용타극막사C／D비치무현저상관성。
Objective To investigate the gene frequency and allele fre-quency of multidrug resistance gene ( MDR1) C1236T, G2677T/A and C3435T of Chinese renal transplant recipients of ethnic Han in Sichuan, and explore the relevance between the gene polymorphisms on tacrolimus and the ratio of blood concentration /dosage in the patients, so as to pro-vide reliable information for personalized tacrolimus administration in kid-ney transplanted patients by pharmacogenomics.Methods Totally 101 healthy volunteers and 56 patients receiving parental kidney transplanta-tion with above 6 -month follow -up were recruited, and gene chips were used to detect the single nucleotide polymorphism ( SNP) of MDR1 C1236T, G2677T/A and C3435T, with randomly selected from 50 sites for DNA sequencing to verify the method of gene chip.To determine the empty stomach blood concentrations of tacrolimus for 56 patients on the 7th, 14th and 30th day, and in the 3rd and 6th month after operation, and then compare the differences of various genotypes in the period of tacroli-mus blood concentration/dosage ratio.Results In the healthy volun-teers, the mutation frequency of MDR1G2677T/A, G2677T/A, C3435T was 43.05%, 14.90%, 40.10% respectively.These alleles frequency mutation resembles 56 cases of renal transplantation patients, which conforms to the Hardy-Weinberg equilibrium by the chi-square analysis.MDR1C1236T, G2677T/A and C3435T polymorphism within 6 months after renal transplan-tation at different time points tacrolimus blood concentration /dose ratio correction difference was not statistically signi-ficant ( P >0.05 ).Conclusion MDR1C1236T, polymorphism G2677T /A and C3435T and kidney transplant patients taking tacrolimus C /D ratio was no significant correlation.