Association of MDR1 gene SNPs and haplotypes with the tacrolimus dose requirements in Han Chinese liver transplant recipients.
Association of MDR1 gene SNPs and haplotypes with the tacrolimus dose requirements in Han Chinese liver transplant recipients.
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中国汉族肝移植受者中 MDR1 基因 SNP 和单倍型与他克莫司剂量需求的关联。
DOI：
10.1371/journal.pone.0025933
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Yu X;Xie H;Wei B;Zhang M;Wang W;Wu J;Yan S;Zheng S;Zhou L
本工作旨在评估他克莫司的C/D比（他克莫司的血浆浓度除以每体重每日他克莫司剂量）与C1236T（rs1128503）、G2677A/T（rs2032582）和C3435T（rs1045642）组合的MDR1基因单倍型之间的关联， 并进一步确定单倍型在汉族肝移植受者口服他克莫司临床药代动力学中的功能意义。首次给药后连续记录1个月他克莫司血药浓度，并提取62例肝移植受者的外周血DNA。对C1236T、G2677A/T和C3435T进行基因分型，并利用PLINK软件进行SNP频率、Hardy-Weinberg平衡、连锁不平衡、单倍型分析和多重检测。比较不同SNP组或单倍型组的C/D比值，p值<0.05认为有统计学意义。连锁研究表明，C1236T、G2677A/T 和 C3435T 在遗传上彼此相关。携带由 C1236T 和 G2677A/T 组合的 T-T 单倍型以及任一位置上的额外 T/T 纯合子的患者将需要更高剂量的他克莫司。不同MDR1基因单倍型组间肝移植受者他克莫司C/D比值差异显着。我们的研究表明，遗传多态性可以作为预测肝移植受者他克莫司 C/D 比值的有价值的分子标记。
This work seeks to evaluate the association between the C/D ratios (plasma concentration of tacrolimus divided by daily dose of tacrolimus per body weight) of tacrolimus and the haplotypes of MDR1 gene combined by C1236T (rs1128503), G2677A/T (rs2032582) and C3435T (rs1045642), and to further determine the functional significance of haplotypes in the clinical pharmacokinetics of oral tacrolimus in Han Chinese liver transplant recipients. The tacrolimus blood concentrations were continuously recorded for one month after initial administration, and the peripheral blood DNA from a total of 62 liver transplant recipients was extracted. Genotyping of C1236T, G2677A/T and C3435T was performed, and SNP frequency, Hardy-Weinberg equilibrium, linkage disequilibrium, haplotypes analysis and multiple testing were achieved by software PLINK. C/D ratios of different SNP groups or haplotype groups were compared, with a p value<0.05 considered statistically significant. Linkage studies revealed that C1236T, G2677A/T and C3435T are genetically associated with each other. Patients carrying T-T haplotype combined by C1236T and G2677A/T, and an additional T/T homozygote at either position would require higher dose of tacrolimus. Tacrolimus C/D ratios of liver transplant recipients varied significantly among different haplotype groups of MDR1 gene. Our studies suggest that the genetic polymorphism could be used as a valuable molecular marker for the prediction of tacrolimus C/D ratios of liver transplant recipients.
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DOI：
10.1016/j.bbapap.2009.02.014
发表时间：
2009-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Fung KL;Gottesman MM
通讯作者：
Gottesman MM
DOI：
10.1097/01.asn.0000073901.94759.36
发表时间：
2003-07-01
影响因子：
13.6
作者：
Anglicheau, D;Verstuyft, CL;Thervet, E
通讯作者：
Thervet, E
DOI：
10.1111/j.1440-1681.2006.04492.x
发表时间：
2006-11-01
影响因子：
2.9
作者：
Hu, Yong-Fang;Qiu, Wen;Zhou, Hong-Hao
通讯作者：
Zhou, Hong-Hao
中国汉族人群的全基因组关联研究确定了系统性红斑狼疮的九个新易感位点
影响因子：
30.8
作者：
Han, Jian-Wen;Zheng, Hou-Feng;Zhang, Xue-Jun
通讯作者：
Zhang, Xue-Jun
影响因子：
6.7
作者：
Anglicheau, D;Thervet, E;Marquet, P
通讯作者：
Marquet, P