title: Association of CTLA-4 gene polymorphism with end-stage renal disease and renal allograft outcome.
abstract: Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is upregulated in effector-T-cells after activation that may alter signal transduction and subsequently cytokine production. The present study was designed to investigate the impact of CTLA-4+49 A>G (rs231775), -318 C>T (rs5742909), -658 C>T (rs11571317), -1147 C>T (rs16840252), -1661 A>G (rs4553808), +6230 A>G (rs3087243) SNPs, and microsatellite (AT)n repeat polymorphism among end-stage renal disease (ESRD), acute allograft rejection (AR), and delayed graft function (DGF) cases. In this regard, 350 ESRD patients and 350 controls were included. Polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis method was used for genotyping of CTLA-4 SNPs, while PCR-polyacrylamide gel electrophoresis method was adopted for studying CTLA4 (AT)n polymorphism. The mutant genotype GG of CTLA-4+49A>G,+6230 A>G, and longer alleles of (AT)n repeats polymorphisms were risk associated with ESRD, AR, and DGF cases. The distribution of haplotype+49G:+6230G and GCTTGG (constructed by using 6 studied SNPs) showed risk association for ESRD, DGF, and AR cases. Further, linkage analysis demonstrated strong to moderate linkage disequilibrium in our study populations. The meta-analysis also revealed risk associations for AR cases against GG genotype of CTLA-4+49A>G SNP, while CTLA-4 -318C>T polymorphism showed no correlation against TT genotype among AR cases. Subsequently, no correlation was established against the CTLA-4 -318C>T, -658 C>T, -1147 C>T, and -1661 A>G SNPs in the promoter region. Survival analysis revealed risk associations against GG genotype of CTLA-4+49A>G, +6230 A>G SNP's with overall survival (OS), and higher hazard for the OS. These results suggested that CTLA-4 variants might be involved in susceptibility to ESRD, AR, and DGF.
authors: 1 Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences , Lucknow, India .
authors: Maneesh Kumar
authors: MK
authors: Misra
authors: Rakesh
authors: R
authors: Kapoor
authors: Shashi Kant
authors: SK
authors: Pandey
authors: Raj Kumar
authors: RK
authors: Sharma
authors: Suraksha
authors: S
authors: Agrawal
mesh_terms: D064591:Allografts; D060908:CTLA-4 Antigen / Q000235:genetics*; D051799:Delayed Graft Function / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006084:Graft Rejection / Q000235:genetics; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000401:mortality; D016030:Kidney Transplantation / Q000401:mortality*; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome
chemical_list: D060908:CTLA-4 Antigen