Zhuo Wu1, Qinxia Xu1, Xiaoyan Qiu2, Zheng Jiao3, Ming Zhang4, Mingkang Zhong1. 1. Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China. 2. Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China. xyqiu@163.com. 3. Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China. zjiao@fudan.edu.cn. 4. Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.
Abstract
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.
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 FOXP3rs3761547, rs3761548, rs3761549, rs2232365, rs2280883, and CCDC22rs2294021 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 FOXP3rs3761548 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 FOXP3rs3761548 polymorphism in renal transplant patients. FOXP3rs3761548 might serve as a biomarker to prevent TAC toxicity and help progression toward individualized therapy of TAC.
Authors: A J Matas; J M Smith; M A Skeans; B Thompson; S K Gustafson; D E Stewart; W S Cherikh; J L Wainright; G Boyle; J J Snyder; A K Israni; B L Kasiske Journal: Am J Transplant Date: 2015-01 Impact factor: 8.086
Authors: I Voineagu; L Huang; K Winden; M Lazaro; E Haan; J Nelson; J McGaughran; L S Nguyen; K Friend; A Hackett; M Field; J Gecz; D Geschwind Journal: Mol Psychiatry Date: 2011-08-09 Impact factor: 15.992
Authors: William S Oetting; Baolin Wu; David P Schladt; Weihua Guan; Jessica van Setten; Brendan J Keating; David Iklé; Rory P Remmel; Casey R Dorr; Roslyn B Mannon; Arthur J Matas; Ajay K Israni; Pamala A Jacobson Journal: Transplantation Date: 2019-06 Impact factor: 4.939