Hongxia Liu1, Qinxia Xu2, Wenyan Huang3, Qi Zhao4, Zhihu Jiang1, Xinyu Kuang3, Zhiling Li1, Huajun Sun5, Xiaoyan Qiu6. 1. Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, 355 Luding Road, Shanghai, 200062, China. 2. Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China. 3. Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, 200062, China. 4. College of Pharmacy, Fudan University, Shanghai, China. 5. Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, 355 Luding Road, Shanghai, 200062, China. shj2049@126.com. 6. Department of Pharmacy, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, China. xyqiu@163.com.
Abstract
PURPOSE: The purpose of this study was to investigate the potential impact of CYP3A4, CYP3A5, and CYP3A7 polymorphisms on the concentration and efficacy of tacrolimus in a cohort of pediatric patients with nephrotic range proteinuria. METHODS: Genetic variants including CYP3A5*3 (rs776746), CYP3A4*1G (rs2242480), rs4646437, and CYP3A7 rs2257401 and rs10211 were detected in 70 pediatric patients with nephrotic range proteinuria. The relationships of dose-adjusted trough concentration (C0) of tacrolimus with corresponding genotypes were investigated. RESULTS: The tacrolimus concentration in patients without CYP3A5*3 A allele was 94% higher than those with A allele (90.7 vs 54.2, P = 0.00006). The CYP3A7 rs2257401 was also associated with the concentration of tacrolimus. The C allele carriers had an obviously lower C0 than the non-carriers (62.4 vs 90.7, P = 0.001). In addition, there were significant differences in tacrolimus concentration among CYP3A7 rs10211 G carriers and non-carriers; the latter had an almost twofold C0 of the former (101.8 vs 59.6, P = 0.0004). CONCLUSIONS: Our study demonstrated the associations between CYP3A5*3, CYP3A7 rs2257401 and rs10211, and tacrolimus concentration in pediatric patients with nephrotic range proteinuria. Children with CYP3A5*3 A, CYP3A7 rs2257401 C, and rs10211 G alleles might need a higher dose of tacrolimus.
PURPOSE: The purpose of this study was to investigate the potential impact of CYP3A4, CYP3A5, and CYP3A7 polymorphisms on the concentration and efficacy of tacrolimus in a cohort of pediatric patients with nephrotic range proteinuria. METHODS: Genetic variants including CYP3A5*3 (rs776746), CYP3A4*1G (rs2242480), rs4646437, and CYP3A7rs2257401 and rs10211 were detected in 70 pediatric patients with nephrotic range proteinuria. The relationships of dose-adjusted trough concentration (C0) of tacrolimus with corresponding genotypes were investigated. RESULTS: The tacrolimus concentration in patients without CYP3A5*3 A allele was 94% higher than those with A allele (90.7 vs 54.2, P = 0.00006). The CYP3A7rs2257401 was also associated with the concentration of tacrolimus. The C allele carriers had an obviously lower C0 than the non-carriers (62.4 vs 90.7, P = 0.001). In addition, there were significant differences in tacrolimus concentration among CYP3A7rs10211 G carriers and non-carriers; the latter had an almost twofold C0 of the former (101.8 vs 59.6, P = 0.0004). CONCLUSIONS: Our study demonstrated the associations between CYP3A5*3, CYP3A7rs2257401 and rs10211, and tacrolimus concentration in pediatric patients with nephrotic range proteinuria. Children with CYP3A5*3 A, CYP3A7rs2257401 C, and rs10211 G alleles might need a higher dose of tacrolimus.
Entities:
Keywords:
CYP3A5; CYP3A7; Nephrotic range proteinuria; Pediatric patients; Polymorphisms; Tacrolimus
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