R Deng1, Y Liao2, Yi Li2, J Tang3. 1. Department of Infectious Disease Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China. 2. Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China. 3. Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China. Electronic address: tjtdr@hotmail.com.
Abstract
BACKGROUND: The purpose of this study is to explore the association of CYP3A5, ABCB1, and CYP2C8 polymorphisms with the risk of developing early kidney impairment in Chinese liver transplant recipients receiving tacrolimus. METHODS: CYP3A5, ABCB1, and CYP2C8 polymorphisms were genotyped in the Chinese liver transplant recipients in the study receiving tacrolimus for at least 2 years by polymerase chain reaction and high-resolution melting method. Serum cystatin C and urine microprotein (α1-microglobulin, microalbumin, transferrin, and immunoglobulin) of liver transplant recipients were used to determine both the status of early renal injury and the lesion part. RESULTS: We documented 3 genotypes of CYP3A5 and ABCB1 and only 2 genotypes of CYP2C8 in our cohort. The levels of cystatin C and all 4 indicators of the urine microprotein in the recipient group were significantly higher than those in the control group (P < .05). The concentrations of transferrin differed significantly in each CYP3A5 genotype group (P < .05). Based on diverse CYP2C8 genotypes, we divided all the recipients into 2 groups: CYP2C8*1*1 group and CYP2C8*3*1 group. The concentrations of α1-microglobulin and cystatin C differed significantly between the 2 groups (P < .05). For CYP2C8*3, the positive predictive value is 68.5% and negative predictive value is 70.2%. For CYP3A5*3, the positive predictive value is 55.3% and negative predictive value is 60.4%. CONCLUSIONS: CYP2C8*3 and CYP3A5*3 appear to be predictive of risk of tacrolimus-induced early renal impairment. CYP3A5*3 was associated with the risk of early renal glomerular lesion, while CYP2C8*3 was associated with the risk of the tubulointerstitial injury. ABCB1 polymorphisms (both C3435T and C1236T) were not associated with the early renal injury in liver transplant recipients.
BACKGROUND: The purpose of this study is to explore the association of CYP3A5, ABCB1, and CYP2C8 polymorphisms with the risk of developing early kidney impairment in Chinese liver transplant recipients receiving tacrolimus. METHODS:CYP3A5, ABCB1, and CYP2C8 polymorphisms were genotyped in the Chinese liver transplant recipients in the study receiving tacrolimus for at least 2 years by polymerase chain reaction and high-resolution melting method. Serum cystatin C and urine microprotein (α1-microglobulin, microalbumin, transferrin, and immunoglobulin) of liver transplant recipients were used to determine both the status of early renal injury and the lesion part. RESULTS: We documented 3 genotypes of CYP3A5 and ABCB1 and only 2 genotypes of CYP2C8 in our cohort. The levels of cystatin C and all 4 indicators of the urine microprotein in the recipient group were significantly higher than those in the control group (P < .05). The concentrations of transferrin differed significantly in each CYP3A5 genotype group (P < .05). Based on diverse CYP2C8 genotypes, we divided all the recipients into 2 groups: CYP2C8*1*1 group and CYP2C8*3*1 group. The concentrations of α1-microglobulin and cystatin C differed significantly between the 2 groups (P < .05). For CYP2C8*3, the positive predictive value is 68.5% and negative predictive value is 70.2%. For CYP3A5*3, the positive predictive value is 55.3% and negative predictive value is 60.4%. CONCLUSIONS:CYP2C8*3 and CYP3A5*3 appear to be predictive of risk of tacrolimus-induced early renal impairment. CYP3A5*3 was associated with the risk of early renal glomerular lesion, while CYP2C8*3 was associated with the risk of the tubulointerstitial injury. ABCB1 polymorphisms (both C3435T and C1236T) were not associated with the early renal injury in liver transplant recipients.
Authors: Tomislav Kelava; Petra Turcic; Antonio Markotic; Ana Ostojic; Dino Sisl; Anna Mrzljak Journal: World J Gastroenterol Date: 2020-03-28 Impact factor: 5.742