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Association of MDR1 gene SNPs and haplotypes with the tacrolimus dose requirements in Han Chinese liver transplant recipients.


ABSTRACT:

Background

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.

Methodology/principal findings

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.

Conclusions

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.

SUBMITTER: Yu X 

PROVIDER: S-EPMC3215699 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Publications

Association of MDR1 gene SNPs and haplotypes with the tacrolimus dose requirements in Han Chinese liver transplant recipients.

Yu Xiaobo X   Xie Haiyang H   Wei Bajin B   Zhang Min M   Wang Weilin W   Wu Jian J   Yan Sheng S   Zheng Shusen S   Zhou Lin L  

PloS one 20111114 11


<h4>Background</h4>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.<h4>Methodology/principal findings</h4>T  ...[more]

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