Association Between Tacrolimus Trough Concentration After Liver Transplant With CYP3A Gene Polymorphisms And Weight Of Donor Liver

Aim: To investigate whether interindividual variation of FK506 trough concentration level after liver transplantation was correlated with CYP3A (CYP3A4, CYP3A5 and CYP3AP1) gene polymorphisms, the expression level of CYP3A4 and CYP3A5 gene mRNA in donor liver, and donor liver weight.Methods: Recorded body weight dates of patients, FK506 dosage and trough concentration level dates, donor liver weight dates. Selected three tag-single nucleotide polymorphisms (SNPs) in CYP3A4 gene. Detected genotypes of these tag-SNPs, rs776746 in CYP3A5 gene and rs2177180 in CYP3AP1 gene by SNaPshot method. Using keeper gene glyceraldehydes -3-phosphate dehydrogenase(GAPDH) as reference gene, detected CYP3A4 and CYP3A5 mRNA expression level in donor liver by Real-Time RT PCR. Calculated graft-to-recipient body weight ratio (GRWR)of each patients. Evaluated whether the polymorphisms of CYP3A4 and CYP3A5 gene, or the expression level of CYP3A4 and CYP3A5 mRNA in donor liver, or GRWR were associated with FK506 trough concentration level/dosage average ratios(C/D ratios) after operation.Results: Compared FK506 C/D average ratios,there were no statistic differences between different groups divided by tag-SNPs genotypes in CYP3A4 gene, no difference was found between high CYP3A4 mRNA expression level group with low group too. If dividing patients by genotypes of rs776746 in CYP3A5 gene, or genotypes of rs2177180 in CYP3AP1 gene, or CYP3A5 mRNA expression level,or GRWR respectively, FK506 C/D average ratios after operation were obvious different between different groups.The average expression level of CYP3A4 mRNA was not different between donor liver groups divided by CYP3A4 tag-SNPs genotypes, but there were obvious difference for the average expression level of CYP3A5 mRNA between donor liver groups divided by CYP3A5 or CYP3AP1 gene polymorphisms. Conclusion: The genotypes of tag-SNPs in CYP3A4 gene or the CYP3A4 mRNA expression level in donor liver did not influence FK506 trough concentration level; The genotypes of rs776746 in CYP3A5 gene and rs2177180 in CYP3AP1 gene, or the CYP3A5 mRNA expression level in donor liver, or donor liver weight influenced FK506 trough concentration level. In order to predict FK506 trough concen -tration level and determine FK506 dosage for a single patient by these information, more researches should be performed.