Association of ABCC2 genetic polymorphism with liver disfunction induced by cyclosporine in Chinese renal transplant recipients

Abstract

Abstract: AIM: To investigate the association between cyclosporine (CsA) induced liver disfunction and multidrug resistance-association protein 2 (MRP2/ABCC2) genetic polymorphisms in Chinese renal transplant recipients.METHODS: 339 renal allograft recipients were included in this study which were all treated by CsA. Two SNPs (rs717620 A/G; rs2273697 G/A) in chr.10 were genotyped. Besides, the CsA whole blood levels of renal transplant recipients were measured by fluorescence polarization immunoassay. All the subjects were divided into three groups according to the liver injury occurrence.RESULTS: The frequencies of rs717620 and rs2273697 mutation allele were 38.89% and 10.72%, respectively. The ABCC2 gene rs717620 SNP, G mutation allele was strongly associated with CsA induced liver disfunction. Compared with the control group, the distribution frequency of the GG genotype was significantly increased in CsA induced liver disfunction group (P<0.05), and that of the AA genotype was significantly increased (P<0.05). The ABCC2 gene rs2273697 polymorphism was not strongly associated with CsA hepatotoxicity. Genotype analysis revealed that there was no significant associations between these two SNPs and cyclosporine trough concentrations. But a positive association between rs2273697 polymorphism and ALT, AST concentrations was obse rved. The risk of disease for homozygous GG carriers was 6-fold higher (OR=6.960, 95%CI:1.636-29.610, P<0.01) in comparison with AA carriers in rs717620 gene. Analysis of haploid showed that compared with individuals carrying AA-AA, the risks of CsA induced liver disfunction after transplantation in the individuals carrying GG-GG and GG-GA were 5.909 and 13.333-fold higher, respectively.CONCLUSION: There is an association between the rs717620 genetic polymorphism in exon 1 of ABCC2 gene and CsA induced liver disfunction. The haploids carrying GG-GG and GG-GA have higher risk to result in CsA induced liver disfunction.

Key words: Cyclosporine, Renal transplant recipients, ABCC2 gene, Liver function

CLC Number:

R969

XIN Hua-wen, LIU Hui-ming, LI Yuan-qi, HUANG Hui, ZHAO Li, YU Ai-rong, LI Qing, WU Xiao-chun, LI Wei-liang, XIONG Lei. Association of ABCC2 genetic polymorphism with liver disfunction induced by cyclosporine in Chinese renal transplant recipients[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(7): 778-784.

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