title: Polymorphisms in CTLA4 influence incidence of drug-induced liver injury after renal transplantation in Chinese recipients.
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.
authors.affiliation: Organ Transplantation Center, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. gyfslm@gmail.com
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Guo
authors.forename: Yu
authors.initials: Y
authors.lastname: Fan
authors.forename: Jianxin
authors.initials: J
authors.lastname: Qiu
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Junwei
authors.initials: J
authors.lastname: Gao
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology; D002681:China / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000453:epidemiology / Q000209:etiology*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D007166:Immunosuppressive Agents