Polymorphisms in CTLA4 Influence Incidence of Drug-Induced Liver Injury after Renal Transplantation in Chinese Recipients |
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| Authors: | Yifeng Guo Yu Fan Jianxin Qiu Yong Liu Junwei Gao Fang Guo |
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| Institution: | 1. Organ Transplantation Center, Shanghai First People''s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.; 2. Department of Pharmacy, Shanghai First People''s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.; 3. Center for Nanomedicine and Translational Medicine, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China.; Oslo University Hospital, Norway, |
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| Abstract: | Genetic polymorphisms in cytotoxic T lymphocyte-associated antigen 4 (CTLA4) play an influential role in graft rejection and the long-term clinical outcome of organ transplantation. We investigated the association of 5 CTLA4 single-nucleotide polymorphisms (SNPs) (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A) with drug-induced liver injury (DILI) in Chinese renal transplantation (RT) recipients. Each recipient underwent a 24-month follow-up observation for drug-induced liver damage. The CTLA4 SNPs were genotyped in 864 renal transplantation recipients. A significant association was found between the rs231775 genotype and an early onset of DILI in the recipients. Multivariate analyses revealed that a risk factor, recipient rs231775 genotype (p = 0.040), was associated with DILI. Five haplotypes were estimated for 4 SNPs (excluding rs733618); the frequency of haplotype ACGG was significantly higher in the DILI group (68.9%) than in the non-DILI group (61.1%) (p = 0.041). In conclusion, CTLA4 haplotype ACGG was partially associated with the development of DILI in Chinese kidney transplant recipients. The rs231775 GG genotype may be a risk factor for immunosuppressive drug-induced liver damage. |
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