The Role of Vitamin D Metabolism Genes and Their Genomic Background in Shaping Cyclosporine A Dosage Parameters after Kidney Transplantation.

Background

Kidney transplantation is followed by immunosuppressive therapy involving calcineurin inhibitors (CNIs) such as cyclosporin A. However, long-term high CNIs doses can lead to vitamin D deficiency, and genetic variations influencing vitamin D levels can indirectly impact the necessary CNIs dosage. This study investigates the impact of genetic variations of vitamin D binding protein (DBP) rs2282679 and CYP2R1 hydroxylase rs10741657 polymorphisms on the cyclosporin A dosage in kidney transplant recipients. Additional polymorphisims of genes that are predicted to influence the pharmacogenetic profile were included.

Methods

Gene polymorphisms in 177 kidney transplant recipients were analyzed using data mining techniques, including the Random Forest algorithm and Classification and Regression Trees (C&RT). The relationship between the concentration/dose (C/D) ratio of cyclosporin A and genetic profiles was assessed to determine the predictive value of DBP rs2282679 and CYP2R1 rs10741657 polymorphisms.

Results

Polymorphic variants of the DBP (rs2282679) demonstrated a strong predictive value for the cyclosporin A C/D ratio in post-kidney transplantation patients. By contrast, the CYP2R1 polymorphism (rs10741657) did not show predictive significance. Additionally, the immune response genes rs231775 CTLA4 and rs1800896 IL10 were identified as predictors of cyclosporin A response, though these did not result in statistically significant differences.

Conclusions

DBP rs2282679 polymorphisms can significantly predict the cyclosporin A C/D ratio, potentially enhancing the accuracy of CNI dosing. This can help identify patient groups at risk of vitamin D deficiency, ultimately improving the management of kidney transplant recipients. Understanding these genetic influences allows for more personalized and effective treatment strategies, contributing to better long-term outcomes for patients.