FOXP3 rs3761548 polymorphism is associated with tacrolimus-induced acute nephrotoxicity in renal transplant patients

• Published in: European journal of clinical pharmacology 2017, Vol.73 (1), p.39-47
• Main Authors: Wu, Zhuo, Xu, Qinxia, Qiu, Xiaoyan, Jiao, Zheng, Zhang, Ming, Zhong, Mingkang
• Format: Article
• Language: English
• Subjects: Adult; Asian Continental Ancestry Group - genetics; Biomedical and Life Sciences; Biomedicine; Female; Forkhead Transcription Factors - genetics; Genotype; Graft Rejection - genetics; Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - blood; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - therapeutic use; Kidney Diseases - chemically induced; Kidney Diseases - genetics; Kidney Transplantation; Kidneys; Male; Middle Aged; Pharmacogenetics; Pharmacology/Toxicology; Polymorphism; Polymorphism, Single Nucleotide; Proteins - genetics; Studies; Tacrolimus - adverse effects; Tacrolimus - blood; Tacrolimus - pharmacokinetics; Tacrolimus - therapeutic use; Toxicity; Transplants & implants; Treatment Outcome
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-016-2140-z

Purpose The purpose of this study was to investigate the potential impact of FOXP3 and CCDC22 gene polymorphisms on efficacy and safety of tacrolimus (TAC) in renal transplant patients. Methods Genetic polymorphisms were detected in 114 Chinese renal transplant patients who were on TAC-based maintenance immunosuppression and were followed up for at least 2 years. The relationships between FOXP3 rs3761547, rs3761548, rs3761549, rs2232365, rs2280883, and CCDC22 rs2294021 polymorphisms and clinical outcomes such as acute rejection, TAC-induced acute nephrotoxicity, and pneumonia were investigated by using Kaplan-Meier estimates and multivariate Cox regression analysis. The influence of these gene polymorphisms on the change in estimated glomerular filtration rate over time was evaluated by linear mixed model. Results Patients with FOXP3 rs3761548 AA and AC genotypes had a 10-fold higher risk for TAC-induced acute nephrotoxicity than those with CC genotype. We did not find any association between other genetic variants and TAC-related outcomes in renal transplant patients. Conclusions Our study demonstrated the TAC-induced acute nephrotoxicity was associated with FOXP3 rs3761548 polymorphism in renal transplant patients. FOXP3 rs3761548 might serve as a biomarker to prevent TAC toxicity and help progression toward individualized therapy of TAC.