Date: Tuesday, May 2, 2017
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Background: Tacrolimus, which plays a backbone in immunosuppressive therapy, has a different effect in absorption according to intraindividual and interindividual variability, and it is a drug requiring monitoring with a narrow therapeutic range. The objective of this study is to investigate genes affecting pharmacological properties as a mentioned, and to compare them with clinical characteristics that the significant genes influence.
Methods: Data from renal transplant recipients receiving tacrolimus were analyzed prospectively between Jan. 2015 and Mar 2016. A total of 55 recipient who were taken tacrolimus as determined by computerized dosing strategy. Dose-adjusted trough blood concentrations (ng/ml per mg/kg) as well as does required to achieve target concentration were compared among the patients. The tacrolimus intraindividual variability (IIV) and coefficient variation (CV) were calculated from trough concentration between 1 and 9 days after transplantation. They were genotyped for one hundred ten genomes.
Result: The mean CV and IIV was 30.6±13.23 %( 10.4~78.0) and 26.1±11.82 %( 8.9~26.09). There was positive correlation between CV and IIV (R 0.8, p-value< 0.001), while IIV and tacrolimus clearance (CL) or volume of distribution (Vd) were negatively related (R -0.319, p-value 0.018, R -0.720, p-value <0.001). There is no significant correlation with dosage of tacrolimus and CV or IIV. The genomic analysis showed several significant new genes polymorphism as following; CACNA1C, CACNA1C-AS1, SLC6A3, CYP3A4, ABCC9, CYP1A2, etc. The significant association was found between CV or IIV and ABCC9 or CACNA1C gene polymorphism. CYP3A4 gene polymorphism was related to dosage of tacrolimus (mg/kg body weight)
Conclusion: ABCC9, CYP3A4, CACNA1C gene polymorphism affected the pharmacokinetics of tacrolimus in renal transplant recipients. Considering these genes polymorphism , further study is needed to achieve a better individualization of immunosuppressive therapy and to quickly reach the target blood concentration.
CITATION INFORMATION: Kim S.-Y, Oh J, Yun S, Jang I.-J, Min S.-I, Cho W, Cho S, Ahn S, Min S.-K, Ha J. Tacrolimus Pharmacogenomics: Association of Genetic Variants with Clinical Factors Including Tacrolimus Requirement, Clearance, Intraindividual Variability, and Coefficient Variation. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Kim S-Y, Oh J, Yun S, Jang I-J, Min S-I, Cho W, Cho S, Ahn S, Min S-K, Ha J. Tacrolimus Pharmacogenomics: Association of Genetic Variants with Clinical Factors Including Tacrolimus Requirement, Clearance, Intraindividual Variability, and Coefficient Variation. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/tacrolimus-pharmacogenomics-association-of-genetic-variants-with-clinical-factors-including-tacrolimus-requirement-clearance-intraindividual-variability-and-coefficient-variation/. Accessed November 20, 2019.
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