Tacrolimus Pharmacogenomics: Association of Genetic Variants with Clinical Factors Including Tacrolimus Requirement, Clearance, Intraindividual Variability, and Coefficient Variation.
1Surgery, Seoul National University College of Medicine, Seoul, Korea
2Clinical Pharmacology, Seoul National University College of Medicine, Seoul, Korea
Meeting: 2017 American Transplant Congress
Abstract number: D98
Keywords: Dosage, FK506, Genomics, Pharmacokinetics
Session Information
Session Name: Poster Session D: Kidney Immunosuppression: Novel Regimens and Drug Minimization
Session Type: Poster Session
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 May 25, 2025.« Back to 2017 American Transplant Congress