title: CTLA4 polymorphisms and de novo malignancy risk 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 five CTLA4 single-nucleotide polymorphisms (SNPs) (rs733618 C/T, rs4553808 A/G, rs5742909 C/T, rs231775 A/G, and rs3087243 G/A) with de novo malignancy in 1463 Chinese renal transplantation (RT) recipients who underwent a 192-month follow-up. Multivariate analyses revealed that recipient rs231775 genotype is significantly associated with tumorigenesis (P = 0.012). Multiplicative interaction between rs231775 AA and possible risk factors of malignancy revealed two significant results: rs231775 AA × primary diseases and rs231775 AA × number of HLA-mismatch. The frequency of haplotype TACAG was significantly higher in the tumor group (17.07%) than that in the nontumor group (1.53%). In addition, aristolochic acid nephropathy (P = 0.003) and the time of discovery of tumor (P = 0.000) also were independently associated with tumorigenesis. Our data show that the CTLA4 genotype rs231775 AA may be one of risk factors for the development of malignancy and haplotype TACAG was susceptible haplotype in Chinese kidney transplant recipients.
authors: Organ Transplantation Center, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors: Yi-feng
authors: YF
authors: Guo
authors: Organ Transplantation Center, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors: Jian-xin
authors: JX
authors: Qiu
authors: Key Laboratory of Systems Biology, Shanghai Advanced Research Institute (SARI), Chinese Academy of Sciences, 99 Haike Road, Shanghai 201210, China.
authors: Fang
authors: F
authors: Guo
authors: Organ Transplantation Center, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, 100 Haining Road, Shanghai 200080, China.
authors: Yong
authors: Y
authors: Liu
authors: Department of Nephrology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, China.
authors: Ming-hua
authors: MH
authors: Shang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006084:Graft Rejection / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016030:Kidney Transplantation / Q000379:methods; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D012307:Risk Factors
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human